24 marzo 2017

Small Cell Lung Cancer (SCLC ): No Treatment Advances in Recent Years .

Small cell lung cancer (SCLC) is an aggressive malignancy with a distinct natural history and dismal prognosis. Given its predisposition for early dissemination, patients are commonly diagnosed with metastatic disease and chemotherapy is regarded as the cornerstone of approved treatment strategies.

However, over the last 30 years there has been a distinct paucity of significant breakthroughs in SCLC therapy. Thus, SCLC is characterized as a recalcitrant neoplasm with limited therapeutic options. By employing well-established research approaches, proven to be efficacious in non-small cell lung cancer (NSCLC), a growing amount of data has shed light on the molecular biology of SCLC and enhanced our knowledge of the “drivers” of tumor cell survival and proliferation.

New therapeutic targets have emerged, but no significant improvement in patients’ survival has been demonstrated thus far.

In a sense, the more we know, the more we fail.

Nowadays this is starting to change and methodical research efforts are underway. It is anticipated that the next decade will see a revolution in the treatment of SCLC patients with the application of effective precision medicine and immunotherapy strategies.

...

Conclusions :

In spite of recent advances in elucidating the aberrant molecular pathways that dictate SCLC oncogenesis, this malignancy remains an important public health problem, leading to the death of approximately 16,000 patients per year in the United States (14). For decades, cytotoxic chemotherapy has remained the backbone of treatment but, while SCLC is a chemo-sensitive disease, experience shows that high response rates are not universally translated into a cure. Nevertheless, it is high time progress was made in SCLC research and we have all the necessary tools at our disposal. Every failure is a lesson learnt, every success a battle fought. Our aim must be to improve the prognosis of patients with SCLC.

We are still on the long journey to Ithaca and should not let the Sirens of excessive optimism distract us from our goal. With determination and cunning we can reach Ithaca. By any means, whatever the final result may be, the entire research process will make us wiser.

“As you set out for Ithaca, hope the voyage is a long one, full of adventure, full of discovery……And if you find her poor, Ithaca won’t have fooled you. Wise as you will have become, so full of experience, you will have understood by then what these Ithakas mean” (The Canon by CP Cavafy, translated by Edmund Keeley and Philip Sherrard).

...


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P.J.: Según los Analistas de EDISON Investment ...  Uno de los Farmacos más relevantes de los últimos 30 años en la I+D para el Tratamiento de SCLC  es el PM01183 ( Lurbi ) . Dichos Analistas Destacan en el reciente Analisis publicado la semana pasada  que PM01183 es Orphan Drug tanto en Ovario como en SCLC  asi como todas las Protecciones que tiene el Farmaco hasta el 2033 :





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PharmaMar . Del 1 al 5 de abril Presentara Nuevos Datos de Yondelis , Aplidin y PM01183 ( LURBI ) en el Congreso Anual de la AACR .

Resultado de imagen de aacr congress 2017Congreso Anual de la AACR del del 1 al 5 de abril de 2017 que se realiza en Washington DC. 

Este Congreso de la “American Association for Cancer Research” (AACR) es un importante foro internacional donde se presentan los últimos avances en terapias dirigidas contra el cáncer y nuevas estrategias terapéuticas.

 El Congreso de la AACR es todo un referente mundial en el ámbito de la investigación sobre el cáncer.

AACR es la Mayor Organización Científica del Mundo en Oncología.

Aplidin Combinado con Gemzar ® (Gemcitabine) de Lilly . Resultados de la Fase I Lymphomas .

Resultado de imagen de gemzarPhase I Dose-Escalation Study of Plitidepsin in Combination with Sorafenib or Gemcitabine in Patients with Refractory Solid Tumors or Lymphomas.

Aspeslagh S, Stein M, Bahleda R, Hollebecque A, Salles G, Gyan E, Fudio S, Extremera S, Alfaro V, Soto-Matos A, Soria JC.

Abstract :

This phase I trial evaluated the combination of the marine-derived cyclodepsipeptide plitidepsin (trade name Aplidin) with sorafenib or gemcitabine in advanced cancer and lymphoma patients. The study included two treatment arms: a sorafenib/plitidepsin (S/P) and a gemcitabine/plitidepsin (G/P) arm. In the S/P arm, patients were treated orally with sorafenib continuous dosing at two dose levels (DL1: 200 mg twice daily and DL2: 400 mg twice daily) combined with plitidepsin (1.8 mg/m, day 1, day 8, day 15, and, q4wk, intravenously).

In the G/P arm, patients with solid tumors or lymphoma were treated at four different DLs with a combination of gemcitabine (DL1: 750 mg/m, DL2-DL4: 1000 mg/m) and plitidepsin (DL1-DL2: 1.8 mg/m; DL3: 2.4 mg/m; DL4: 3 mg/m). Both agents were administered intravenously on day 1, day 8, day 15, and, q4wk. Forty-four patients were evaluable for safety and toxicity. The safety of the combination of plitidepsin with sorafenib or gemcitabine was manageable.

Most adverse events (AEs) were mild; no grade 4 treatment-related AEs were reported in any of the groups (except for one grade 4 thrombocytopenia in the gemcitabine arm). The most frequently reported study drug-related (or of unknown relationship) AEs were palmar-plantar erythrodysesthesia, erythema, nausea, vomiting, and fatigue in the S/P arm and nausea, fatigue, and vomiting in the G/P arm. In the S/P arm, one dose-limiting toxicity occurred in two out of six patients treated at the maximum dose tested (DL2): palmar-plantar erythrodysesthesia and grade 2 aspartate aminotransferase/alanine aminotransferase increase that resulted in omission of days 8 and 15 plitidepsin infusions.

In the G/P arm, one dose-limiting toxicity occurred in two out of six patients at DL4: grade 2 alanine aminotransferase increase resulted in omission of days 8 and 15 plitidepsin infusions and grade 4 thrombocytopenia.

The recommended dose for the combination of plitidepsin with sorafenib was not defined because of a sponsor decision (no expansion cohort to confirm) and for plitidepsin with gemcitabine, it was 2.4 mg/m plitidepsin with 1000 mg/m gemcitabine. In the S/P group, objective disease responses were not observed; however, disease stabilization (≥3months) was observed in four patients.

In the Gemcitabine Group, two Lymphoma Patients Showed an Objective Response ( Partial Response and Complete Response ) and Nine Patients showed Disease Stabilization (≥3months). Combining plitidepsin with Gemcitabine and Sorafenib is feasible for advanced cancer patients; some objective responses were observed in heavily pretreated lymphoma patients.

#HorizonteAntártida : La Aventura de la Ciencia . Distantcom : Los Alegres buceadores del bentos antártico .

Publicado por: 23 marzo, 2017 .

Especial para Efeverde, por @ValentinCarrera a bordo del Hespérides.- 


Imagen relacionada“Si nos cargamos la biodiversidad, nos cargamos también moléculas no descritas, potencialmente beneficiosas”, me explica Conxita Ávila, mientras inspecciona uno de sus botes de muestras, de espaldas a la cámara para no salir en las fotografías, de modo que retrato a otros miembros de su equipo, miembras diría aquí la ilustre exministra, porque es el único equipo fifty fifty chicos-chicas, y el único de los casi treinta proyectos de esta campaña dirigido por una mujer.

Cuando hablamos de igualdad, significa que la paridad rompa el techo de cristal y alcance los puestos de mando: una mujer (o dos si incluimos a la colombiana Rosa Acevedo) entre treinta IPs, investigadores principales, no es para echar cohetes. Queda dicho.
Había oído hablar de Conxita Ávila bastante antes de conocerla: cuando llegó, en enero, le precedía una fama contundente. El runrún que los periodistas estamos obligados a sintonizar traducía ecos de una mujer de carácter fuerte y muy catalana, dos virtudes que levantan ampollas en un mundo masculino y con sello estatal.

Pero la ciencia no tiene fronteras, como demuestra el proyecto DISTANTCOM que lidera Conxita Ávila en esta campaña, su novena en la Antártida, con investigadores de la Universidad de Barcelona. Uno de los equipos más jóvenes y dinámicos, y añadiré por mi cuenta alegres y divertidos, formado por Carlos Angulo, Rafael Martín, Joana Vicente, Blanca Figuerola, Joan Giménez, Elisenda Ballesté y Conxita Ávila. Biólogos y oceanógrafos enamorados del misterioso fondo submarino.


En ese fondo que los mortales solo podemos conocer a través de sus fotos y vídeos, habita todo un mundo vegetal y animal, infinitas comunidades de algas, erizos, estrellas, esponjas, corales, briozoos, moluscos: todos estos organismos forman el bentos, no tan popular como los pingüinos y las focas, pero imprescindible para la vida oceánica: el bentos es un eslabón clave en la cadena trófica, de modo que sin ese secreto conglomerado vegetal y animal, no habría krill ni pingüinos ni ballenas.


Durante su estancia en Isla Decepción, arropados por el trabajo formidable de los soldados de la Base Gabriel de Castilla, las buceadoras y buceadores de DISTANTCOM se sumergen cada día a 20 ó 25 metros de profundidad, con temperaturas de 0º a -2º, para tomar muestras de ese bentos marino, que inmediatamente son trasladadas para su estudio, en vivo, en el laboratorio húmedo instalado en la propia Base. El laboratorio helado, a temperatura ambiente, donde converso con Conxita Ávila, y donde Joan y Blanca me muestran sus experimentos con líquidos de colorines.

Tenemos cuatro líneas de investigación —explica la doctora Ávila— :

1) Ecología química, extraer productos naturales, estudiar su papel ecológico y su posible aplicación farmacológica, que puede derivar en alguna futura patente;
2) Biodiversidad y efectos del cambio climático en estas comunidades bentónicas;
3) Evolución y filogeografía: contribuir al mejor conocimiento de la distribución de las distintas especies;
4) Ecología trófica, cómo funciona la cadena alimenticia.

...


#HorizonteAntártida: La Aventura de la Ciencia. Distantcom: Los alegres buceadores del bentos antártico

Azar ... La Principal Causa del Cáncer .

Una célula cancerosa. Dos tercios de los cánceres no pueden prevenirse con el estilo de vida; la detección precoz es más esencial que nunca .
JAVIER SAMPEDRO /// Madrid 23 MAR 2017 .

Tradicionalmente se ha pensado que las mutaciones que causan el cáncer provienen de dos fuentes principales: la herencia y el ambiente (humo del tabaco, radiación ultravioleta de la luz solar y muchas otras). Un macroestudio coordinado por genetistas de la Johns Hopkins confirma ahora que no es así: dos tercios de las mutaciones cancerosas provienen de errores al azar en el proceso de replicación del ADN. Solo el tercio restante se debe a la herencia y al ambiente. Este hecho tiene importantes consecuencias para la prevención y tratamiento precoz de cada tipo de cáncer.

El mismo consorcio que publica estos resultados en Science, coordinado por Cristian Tomasetti y Bert Vogelstein, de la facultad de medicina pública Bloomberg de la Universidad Johns Hopkins en Baltimore (un nodo de la genómica internacional del cáncer), ya presentó hace dos años unas conclusiones similares. El megaproyecto ha obtenido ahora evidencias nuevas que las refuerzan, y que revelan nuevas claves que serán valiosas para los oncólogos que tratan a pacientes. Se basan en un nuevo modelo matemático y en datos epidemiológicos de medio planeta.

El trabajo no implica que haya que bajar la guardia sobre los factores ambientales cancerígenos. “Es bien sabido”, explica Tomasetti, “que debemos evitar factores ambientales como fumar para reducir el riesgo de cáncer; pero es menos conocido que, cada vez que una célula normal se divide y duplica su ADN para generar dos células nuevas, comete múltiples errores”. El genoma humano tiene 3.000 millones de bases (las letras del ADN gatacca…) y, pese a que la fidelidad del sistema de replicación es muy alta (menor a un error en un millón), queda mucho margen para generar mutaciones aleatorias.

...

23 marzo 2017

Genomica SAU . Suministro de reactivos y material fungible para la detección del VPH .

Expediente B2017/002703 KITS DETERMINACIÓN VPH .

Resultado de imagen de genomica sau VPHEstado de la licitación: Adjudicada

Organismo que lo promueve: Consejería de Sanidad

Descripción:
Suministro de reactivos y material fungible para la detección del VPH (1584 determinaciones) de los tipos de alto riesgo oncogénico, con genotipado individual y diferenciado de los mismos, así como el mantenimiento de equipos por un periodo de 15 días.

Código de expediente: B2017/002703

Tipo de contrato: Suministros

Tipo de tramitación: Ordinaria

Procedimiento de contratación: Contrato menor

Importe máximo estimado sin IVA: 17990,00 euros

CPV: 33694000-1

Inicio de la publicación: 22 de marzo de 2017, 13:10
Última actualización: 22 de marzo de 2017, 13:10 .


Número de invitaciones: 1

Número de ofertas: 1

Aprobación del gasto:

Fecha de aprobación: 22 de marzo de 2017
Importe de la oferta seleccionada sin IVA: 17989,20 euros .


Adjudicatario: GENOMICA S.A.U

Situación de la I+D farmacéutica en España .

Situación de la I+D farmacéutica en EspañaPharma Market , 21 Marzo 2017 .

La industria farmacéutica es uno de los sectores más innovadores, caracterizado por utilizar una tecnología de producción avanzada y realizar una investigación de calidad con personal altamente cualificado.

Según el informe “Estadística sobre Actividades de I+D 2015” del INE, el gasto en I+D creció en 2015 un 2,7% respecto a 2014, lo que supuso el 1,22% del PIB, concentrando la industria farmacéutica el 8,6% del gasto total en dicho año.

Según los últimos datos disponibles, el 79,5% de las empresas farmacéuticas realizó actuaciones innovadoras en el periodo 2013-2015, por lo que la industria farmacéutica se encuentra en un puesto privilegiado en el ranking de “porcentaje de empresas con actividades innovadoras”.

La industria farmacéutica española es intensiva en I+D+i, lo que la sitúa en una posición clave para contribuir al crecimiento futuro de la economía en su conjunto, dadas sus características propias como motor de desarrollo.

Según los últimos datos de la Federación de Asociaciones de la Industria Farmacéutica Europea (EFPIA), España tiene cada vez una mayor importancia en materia farmacéutica dentro del entorno europeo, consolidándose como el sexto mercado más importante del continente en generación de empleo (tras Alemania, Francia, Reino Unido, Italia y Suiza), el quinto más importante en volumen de ventas (tras Alemania, Francia, Italia y Reino Unido), y el séptimo mercado de la Unión Europea en términos de producción (tras Suiza, Alemania, Italia, Francia, Irlanda y Reino Unido).

Ya existe una prueba para calcular el riesgo de Alzheimer's .

Ya existe una prueba para calcular el riesgo de Alzheimer'sDe acuerdo a investigadores de San Diego y San Francisco .

22 de Marzo 2017

Los investigadores de la Facultad de Medicina de la Universidad de California en San Diego (UCSD) y de la Universidad de California en San Francisco (UCSF) han creado una prueba genética que puede calcular el riesgo específico de un paciente Del Alzheimer.

El método busca 31 marcadores genéticos, recolectados de más de 70.000 individuos, incluyendo pacientes que padecen Alzheimer, así como pacientes ancianos sanos.

"Prevenir el desarrollo de los síntomas de la demencia es el santo grial de la investigación de Alzheimer, pero para tener éxito primero necesitamos métodos precisos para predecir quién tiene más probabilidades de desarrollar la enfermedad” dijo James Pickett, jefe de investigación de la Alzheimer's Society en un informe publicado por The Guardian.

Cabe señalar que la puntuación alta en esta prueba genética no significa automáticamente que alguien va a desarrollar Alzheimer. Tampoco implica que el puntaje bajo significa que alguien sería considerado inmune a la enfermedad. La genética es uno de los varios factores que determinan el riesgo de una persona para desarrollar cualquier enfermedad, incluyendo Alzheimer.

"Desde una perspectiva clínica, el [examen] proporciona una novedosa manera no sólo para evaluar el riesgo de desarrollar la enfermedad de Alzheimer, sino también para predecir la edad de inicio de la enfermedad", dijo el autor principal, Anders Dale, de la Facultad de Medicina de la Universidad de California de San Diego.

EEUU investiga 9 muertes por un tumor asociado a prótesis mamarias .

Redacción | A Coruña 23.03.2017 .

La Federación estadounidense de Alimentos y Fármacos (FDA) ha informado de la muerte de nueve mujeres a causa de un tipo de cáncer que se vincula con la implantación de prótesis mamarias. Todas las víctimas sufrieron un linfoma anaplástico de células grandes que afecta al sistema inmune y aparece en la piel y los ganglios linfáticos, según informó la CNN, donde aseguran que las autoridades sanitarias de Estados Unidos investigan todavía lo sucedido.

Desde la FDA reconocen que el riesgo de sufrir este tipo de tumores es bajo, pero que aumenta en quienes se han implantado prótesis mamarias. Desde 2011 este organismo realiza un seguimiento de los casos para ver posibles complicaciones. Desde entonces se recibieron 359 informes de pacientes con este tipo de linfoma, de ellas nueve muertes y todas las víctimas se habían implantado prótesis de mama para aumentar su pecho.

22 marzo 2017

Yondelis . Nuevo Ensayo Clinico ( Fase Ib ) Sponsorizado por el Institut Bergonié con la Collaboración de AstraZeneca y PharmaMar .

Resultado de imagen de institut bergonié

Trabectedin Combined With Durvalumab (Human Monoclonal Antibody) in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas. (TRAMUNE) .


View of NCT03085225 on 2017_03_20

ClinicalTrials Identifier: NCT03085225
Updated: 2017_03_20 .


Descriptive Information :

Brief title :

Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.



Official title :

Resultado de imagen de astrazeneca
Trabectedin Combined With Durvalumab (MEDI4736) in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas. A Phase Ib Study.



Brief summary : 

A Phase Ib trial study of trabectedin when prescribed in combination with durvalumab in locally advanced/unresectable soft-tissue sarcoma and ovarian carcinomas.

Detailed description :



Resultado de imagen de pharmamar i+dThis is a Multicenter, Prospective Phase Ib Trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Trabectedin given with Durvalumab  ,followed by two expansion cohorts once the MTD is established.
Administrative Data :

Organization name : Institut Bergonié
Organization study ID : IB2016-02
Sponsor : Institut Bergonié
Collaborator : AstraZeneca
Collaborator : PharmaMar

...

21 marzo 2017

CNIO and PharmaMar Have Signed a Collaboration Agreement to Identify New Anti-Tumour Therapies from The Marine Environment.

CNIO y PharmaMar han Rubricado un Acuerdo de Colaboración para Comenzar a Realizar Nuevos Ensayos de Cribado para Caracterizar el Potencial Antitumoral de Compuestos de Origen Marino.

CNIO y PharmaMar colaborarán para identificar terapias antitumorales de origen marino

PHARMA MARKET , 21 Marzo 2017 .
Resultado de imagen de cnio
La firma se ha realizado en la sede del CNIO, y ha contado con la presencia de la doctora María A. Blasco, directora del CNIO; Carmen Vela Olmo, secretaria de Estado de Investigación, Desarrollo e Innovación y Presidenta del Patronato del CNIO; y José María Fernández Sousa-Faro, Presidente de PharmaMar.
Resultado de imagen de solos podemos hacer tan poco juntos podemos
El acuerdo contempla que el CNIO proporcionará el conocimiento y las herramientas desarrollados por distintos grupos de investigación del Centro, en particular el Programa de Terapias Experimentales, que tiene por objetivo el descubrimiento temprano de fármacos que identifiquen nuevos agentes terapéuticos para el tratamiento del cáncer.


Además, se realizarán estudios basados en el uso de modelos celulares procedentes de distintos tumores así como la plataforma de células madre tumorales del CNIO. Con especial ahínco se estudiará el cribado fenotípico y la modulación de dianas terapéuticas ya identificadas por el CNIO.
Resultado de imagen de pharmamarPor su parte, PharmaMar proporcionará al CNIO tanto el acceso, como los datos y material científico, de los compuestos puros y de la biblioteca de organismos marinos para trabajar conjuntamente en la detección de nuevas dianas terapéuticas frente a diferentes tipos de tumores.
Blasco ha comentado que “este acuerdo con PharmaMar, compañía de referencia en el sector, pone de manifiesto la apuesta del CNIO por la colaboración con la industria para transferir los resultados de investigación a productos y servicios que beneficien a los pacientes y por tanto el Sistema Nacional de Salud”.
Sousa-Faro ha añadido: “España se sitúa entre los diez primeros países del mundo en la lucha contra el cáncer. Para nosotros invertir en I+D es clave para poder avanzar en el conocimiento de la ciencia. Firmar un acuerdo de colaboración con el CNIO, centro puntero y de referencia internacional en la investigación contra el cáncer, significa un paso más para poder seguir a la vanguardia y poder dar respuesta a necesidades médicas no cubiertas que necesitan una solución”.

PharmaMar, a las puertas de activar otra clara señal de fortaleza .

JM. Rodriguez // 21 Marzo 2017 // Bolsamania .

Por encima de la resistencia de los 3,2 euros presentaría el camino despejado hasta los máximos de 2015, en los 4,41 euros.

Tras las alzas de las últimas sesiones tenemos a los títulos de PharmaMar a las puertas de la resistencia, antes soporte, de los 3,20 euros. 

Este nivel funcionó como soporte en agosto de 2015 y como resistencia en abril de 2016. Recientemente el título marcó un máximo en los 3,155 euros y desde ahí se giró de nuevo a la baja. 

De lo que se puede deducir con facilidad que por encima de los 3,2 euros, con holgura y en velas semanales, tendríamos una clara y contundente señal de fortaleza que puede ser la antesala, con sus lógicas correcciones intermedias, de un movimiento en busca de los máximos de 2015 en los 4,40 euros.

Luis Mora (PharmaMar): "La Compañía hoy está muy Infravalorada... por Comparables y por Fundamentales" /// "La Estrategia de la Compañía pasa por crear una red de ventas en Estados Unidos" .

Nieves Amigo Bolsamania | 21 mar, 2017 .

Resultado de imagen de luis mora pharmamar*.- El Director General de PharmaMar afirma que están cumpliendo con sus planes y que esperan que 2017 sea un buen año .
*.- "PM1183 es la palanca que nos va a permitir crear esa infraestructura en Estados Unidos y recoger un importante EBITDA" .
*.- Esperamos Poder Pagar Dividendo en un Futuro no muy Lejano .
*.- La aprobación de Aplidina o el resultado del ensayo de cáncer de ovario para PM1183 son dos de los hitos más importantes para este año .

*.- "Estamos cumpliendo los plazos en cuanto a ensayos, que esperamos que sean positivos para poder presentar los dosieres. Los plazos van en perfecta armonía con la estrategia" .
*.- Mora confía en que los acontecimientos de 2017 hagan que el valor cumpla con los pronósticos de los analistas, que les dan un potencial de subida de más del 80% .

2017 podría ser el año en el que PharmaMar por fin despegara tras el letargo que vivió en bolsa en 2016 y después de las fuertes caídas que experimentó a finales de 2015. Hay acontecimientos importantes -que deberían llegar durante la segunda parte del año y que tienen que ver con dos de sus principales productos, Aplidina y PM1183- que prometen animar a la acción. El riesgo: no cumplir con el calendario y decepcionar al mercado.

De momento, "vamos en plazo", avisa Luis Mora, director general de esta biotecnológica que, como dato curioso, cuenta con tres ex ministros en su Consejo de Administración.

Resultado de imagen de luis mora pharmamarPregunta (P.): 2,3 millones, eso es lo que dicen los analistas que ganará PharmaMar en 2017. ¿Saldrán de pérdidas este año?

Respuesta (R.): 2017 va a ser un año muy importante. A finales de año tendremos la opinión de la EMA (Agencia Europea de Medicamentos) para la aprobación de Aplidina, tendremos también los resultados del ensayo pivotal de cáncer de ovario para PM1183 y, si es positivo, empezaremos a preparar el dosier tanto para la FDA (Food and Drug Administration) como para la EMA. Con los acuerdos que ya hemos hecho, como el de Chugai para Japón, con la evolución positiva que prevemos para las ventas, esperamos que sea un buen año. Por otro lado, la inversión en Investigación y Desarrollo (I+D) absorberá bastantes recursos, pero esperamos que sea un buen año, aunque nunca damos guidance (previsiones) de resultados.

P.: En bolsa, los expertos les dan el mayor potencial de subida de todas las compañías del mercado español, de más del 80%. ¿Esperan que, con todos estos acontecimientos que ha mencionado para este año, el valor registre, al menos, parte de esa subida estimada?

R.: Al final el mercado tiene que reflejar los buenos resultados que estamos obteniendo. La compañía hoy está muy infravalorada... por comparables y por fundamentales. Ese potencial de subida se tiene que dar con todos los proyectos y todos los ensayos que están en marcha. Y más con la estrategia de la compañía, que es crear una red de ventas en Estados Unidos, que es el 46% del mercado mundial en oncología. Hemos sido capaces de hacerlo en Europa y pensamos que estamos capacitados para hacerlo en Estados Unidos. PM1183 es la palanca que nos va a permitir crear esa infraestructura en Estados Unidos y recoger un importante EBITDA.

P.: De todos los hitos que ha enumerado para este año 2017, ¿cuál diría que es clave y que sería una gran decepción si no llegase a cumplirse?

R.: No hay uno que resaltar. La aprobación de Aplidina por parte de la EMA -es nuestro segundo producto tras el Yondelis- es importante. El ensayo positivo de ovario para PM1183 es importante. Posibles licencias que pueden venir a lo largo del año... Yo no nombraría uno, sino los tres.

Resultado de imagen de luis mora pharmamarP.: Sigamos hablando de su evolución en bolsa. El último gran batacazo de PharmaMar tuvo lugar entre octubre de 2015 y principios de 2016 y ustedes pidieron a la CNMV que investigara si había habido manipulación. Les dijeron que no y recurrieron. ¿Qué les contestó finalmente la CNMV?

R.: Todavía nada. Fue muy sorprendente porque, además, con la aprobación de Yondelis en el año 2015 en Estados Unidos, la acción perforó los 4 euros. Estaba todavía lejos de lo que nosotros entendemos que es su valoración, pero estábamos muy contentos porque por fin parecía que se estaba empezando a reflejar en el valor. A raíz de ahí, en una actuación incomprensible, empezó a haber unas caídas brutales de la acción y detectamos unos movimientos no claros. Además, observamos una forma de atacar al valor inusual, más si cabe cuando había habido una noticia buenísima y esperada desde hacia muchos años. Lo pusimos en manos de las autoridades y la primera contestación fue que no. Hemos recurrido y ahí estamos.

P.: En Estados Unidos, usted ha dicho que hay incertidumbre y que no es momento de salir a bolsa. Además, la última subida de tipos de la Fed no es la mejor noticia para el sector de biotecnología. ¿Descartan este proyecto para 2017?

R.: Estamos trabajando en ello pero todavía no tenemos fecha. No sé si será a finales de este año o si será el año que viene, pero ni mucho menos se ha descartado. Creo que el mercado americano es un mercado donde compañías como la nuestra tienen que estar por muchos motivos, por visibilidad, por especialización de analistas, bancos de inversión... Cuando haya una ventana importante que cree valor para el accionista, allí iremos.

P.: El tema de una OPA sobre la compañía es recurrente, y más a los precios a los que cotizan. ¿Ese interés que dice el presidente de PharmaMar que han demostrado “algunos”, proviene de España o del extranjero?

R.: Esto es algo que nosotros nunca comentamos. Una compañía como la nuestra, cotizando en España con la capitalización de mercado que tenemos, infravalorada... Es una compañía muy barata. Entiendo que hoy en día es una compañía apetecible para algunas compañías del sector. El riesgo esta ahí.

Resultado de imagen de luis mora pharmamarP.: La estrategia de PharmaMar, que repiten como un mantra, es tener tres productos -Yondelis, Aplidin y PM1183- en cuatro años para cinco indicadores. ¿Van en plazo o temen decepcionar al mercado?
R.: Vamos en plazo. Estamos cumpliendo los plazos en cuanto a ensayos, que esperamos que sean positivos para poder presentar los dosieres. Los plazos van en perfecta armonía con la estrategia.

P.: La mayoría de los analistas aconsejan comprar PharmaMar pero también están los que no confían en ustedes y tienen opiniones tan tajantes como las que dicen que ofrecen "poca claridad o transparencia en los datos clínicos". ¿Por qué creen que hay tanta polaridad en las opiniones hacia ustedes?

R.: Yo creo que sobre todo esto ocurre en España y es algo sorprendente. El año pasado hicimos más de 280 one to one (encuentros cara a cara con inversores) por EEUU y por toda Europa y la verdad es que no existe esa dicotomía, esa diferencia. En cuanto a la transparencia, es total, los datos son públicos. Las fases III son más largas, duran más, pero cuando se tienen los datos, se publican. Otra cosa es que se entienda o que en España muchos inversores quieran saber más a corto plazo, pero es que este negocio es así, los ensayos clínicos duran lo que duran.

P.: Ese interés de los inversores españoles por saber más a corto plazo también se nota en su evolución en bolsa. Da la impresión de que ustedes se mueven a golpe de noticia, sin que se valore el largo plazo.

R.: Claro, esa es la diferencia con un inversor americano. De las 170 compañías que están cotizando en el Nasdaq Biotech Index, tan solo un 10% tiene un EBITDA positivo, el resto tiene EBITDA negativo durante años, pero la creación de valor se percibe en cuanto que van pasando de fase y van publicando los datos en los congresos. Entender ese valor de los productos en las aplicaciones clínicas no siempre es sencillo. Pero, afortunadamente, es cierto que se está aumentando este nivel de conocimiento también en España entre muchos inversores. También es cierto que este 'cortoplacismo' que existe aquí se debe mucho a la tradición inversora que hay en España, que plantea que los resultados deben dejar un dividendo. En la cultura nuestra, ese dividendo es importante...

P.: Y ustedes el dividendo lo tienen por ahora descartado...

R.: Hemos dado EBITDA negativo, no podemos dar dividendo, pero sí esperamos que, con toda esta evolución de la cartera, en un futuro no muy lejano, se pueda pagar dividendo, obviamente.

Pharma Mar Vuelve a Tratar de Romper Resistencia .

Publicado el 20 de Marzo de 2017 por Invertir y Especular .

La acción lleva tirando fuerte tres sesiones con volumen tras doble suelo en zona cercana a 2.6, pero entre 3 y 3.2 tiene una fuerte resistencia, en nuestro último comentario decíamos que si la rompía hasta 4 euros no había nada a su paso. 


Noten como cada vez arranca desde más arriba pero muere en el mismo sitio sus impulsos, en realidad quien compró el abril del año pasado simplemente está a precio. 

A ver si de una vez por todas se deshace de este nivel de control, no nos parece casualidad desde luego que de 3-3.20 no se pase.





20 marzo 2017

Fernández-Sousa: "Los Nuevos Fármacos Pueden Transformar la Actual PharmaMar" . "Estamos baratos en Bolsa; los analistas de Sfifel nos valoran en 6 euros la acción" .

POR A. MEDINA // JM Cadenas // Expansion  /// 19/03/2017 .

..
... En 2016 solo se pudieron Registrar 6 de los 30 millones del acuerdo con Chugai. El grupo sólo puede anotarse este pago como ingreso según los avances de los ensayos clínicos. 

"Por 17 días el dinero entra en enero y eso hace que 2016 salga perjudicado en la foto. Pero este año parte con un regalo de 24 millones", destaca el
presidente de PharmaMar.

"El PM1183 es un fármaco que puede cambiar totalmente la actual PharmaMar", afirma el presidente de la biofarmacéutica, que también trabaja en nuevas indicaciones de este compuesto para otros tumores, como el cáncer de mama. Mientras avanza también en los ensayos de otros productos como Aplidina (mieloma múltiple), PM184 o, a través de Sylentis, en un medicamento para el síndrome de ojo seco, PharmaMar se reservará la comercialización del PM1183 en Estados Unidos (casi la mitad del mercado oncológico mundial) creando una red propia, sobre todo en las costas, Houston y Chicago, que concentran el 75% del mercado. Para ello, fichó en noviembre a Pascar Besman como chief operating officer en Nueva York, "que nos ayudará a tener más presencia allí, tanto desde el punto de vista comercial como de relaciones con inversores y bancos de inversión". Aunque no descarta un acuerdo de copromoción con una gran farmacéutica "si hay una buena oferta". PharmaMar lo venderá en Europa a través su red propia donde comercializa Yondelis y que se ha mostrado dispuesto a abrir a una biotech americana o japonesa "para vender un producto de 50 millones o 100 millones".

La acción de PharmaMar subió un 8% en 2016, frente a la caída del 2% del Ibex y el 21% del Nasdaq Biotech. Sin embargo, Fernández-Sousa mantiene que está infravalorada, con un precio que no supera los tres euros. "Estamos escasos de analistas expertos en el sector de biotecnología, pero Stifel nos valora en unos 6 euros", indica. PharmaMar calcula que, sólo el acuerdo con Chugai, cifra el PM1183 en entre 1.000 millones y 1.300 millones, "el doble de nuestra capitalización. Además, en el grupo destacan cómo la Bolsa no refleja el valor cuando en el Nasdaq algunas biotech americanas con fármacos en fase experimental capitalizan hasta 7.000 millones de dólares, mientras que PharmaMar ya vende Yondelis para dos indicaciones y, si se cumplen las previsiones, podría tener a corto plazo tres productos aprobados para cinco indicaciones .

PharmaMar . Corporate Presentation March 2017 . El Inicio de la Fase III Mama del PM01183 ( Lurbinectedin ) ... Mas Cercano .

Link : XXXXX 27 Pages .


...

17 marzo 2017

EDISON INVESTMENT Pone en Valor cada una de las " Piezas " que Conforman el Grupo PharmaMar que sumadas dan un Valor de 1.286.800 euros . Y le Dan a la Compañía un Precio Objetivo de 5,79 euros .

Los Analistas de Edison Investment desglosan el valor del Lurbinectedin ( PM1183 ) y lo valoran en 3,61 euros por si solo .


PharmaMar‏ . Reunión / Conference // Slingshot para tratar los detalles de un año crucial para nosotros.


Make Informed Investment Decisions with Affordable Access 





Slingshot members are talking to management! The topic is:

A conversation with PharmaMar's Director of Oncology, Newly Hired COO, and Director of Capital Markets to discuss the upcoming pivotal year for the firm.

Ticker(s): PHM.MC, TSRO, CLVS .

Who's the expert?

Resultado de imagen de pharmamar
* Luis Mora Capitán - Managing Director, Oncology Business Unit.

* Pascal Besman - Chief Operating Officer.

* José Luis - Director, Investor Relations & Capital Markets .



Sponsored By: PharmaMar  (OTCPK:PHMMF) .

PharmaMar is a company focused on oncology and committed to research and development which takes inspiration from the sea to discover molecules with antitumor activity. We are an integrated company that seeks innovative products to provide healthcare professionals with new tools to treat cancer.
PharmaMar’s commitment to patients and to research has made it a world leader in the discovery of antitumor drugs of marine origin.

This interview was conducted by Joe McCann, CEO of Slingshot Insights.

Besman: Hello.
Slingshot: Hi, this is Colleen with Slingshot Insights. Hi, do I have Pascal and the rest of the management team on?
Besman: Yep, we're all here.
Mora: Hello.
Luis: Hello.
Slingshot: Hi, everyone.
Mora: Hi.

Slingshot: Gentlemen, thanks so much for taking the time for this call today. We're really looking forward to learning more about PharmaMar and its product pipeline in the oncology space. For compliance purposes, I'd just like to confirm a few key points, which I'll quickly read through and then each of you can grant your verbal consent at the end.
So first, this call is being recorded and a transcript of the call will be available to members of the Slingshot community. Second, you attest that you will not disclose any material nonpublic information or information that will break any confidentiality agreements by which you are bound. So, Pascal, Luis, and José, do you agree to these terms?
Besman: Yes.
Luis: Yes.
Mora: Yes.

Slingshot Admin: Excellent. And Joe, as the call leader, you're also required to keep any material nonpublic information confidential. If you are currently a public company employee or have been employed by a public company within the last 12 months, you attest that you will not share any material, nonpublic information or information that will break any confidentiality agreements by which you are bound. Do you agree to these terms, Joe?

Slingshot: Yes, I do.

Slingshot Admin: Wonderful. Additionally, I'd like to note that this call is intended for informational purposes only. Not investment advice. The content of this call, including any and all information provided regarding individual securities or industries do not constitute financial, legal, or tax advice. All participators are on mute on this phone call with the exception of the PharmaMar management team, as well as Joe, the Call Leader. And with that, I'll let you guys take it away.

Slingshot: Thank you, Colleen. Hi, guys. Good afternoon to you. Thank you for getting on the phone with us today. I'm looking forward to this. Maybe just to give everyone a very quick background, I have your positions at PharmaMar listed on the project page, but if we could just go through and maybe just do 30 seconds on your roles at the company and how long you've been there, before we get into the conversation.

Resultado de imagen de jose luis moreno pharmamarMora: Well hello. Good morning. I'm Luis Mora. I'm the Managing Director, Oncology Unit, at PharmaMar. I joined team PharmaMar in the year 2000. For six years I was CFO at PharmaMar. In 2007, I was nominated Deputy General Manager, in early 2008, Managing Director in PharmaMar's Oncology area. Before PharmaMar, I worked on a team with the Montedison group in Italy, in the all different pharmaceutical and chemical areas. I was a financial consultant for the group, and my first role I worked in Barcelona at Zambón Pharmaceutical as the Financial Controller, and was CFO in Zambón, Portugal. I've had more than 32 years experience in this business, in pharmaceutical and biotech.

Slingshot: Thank you for coming on.
Luis: Good afternoon. My name is José Luis Moreno. I'm the Capital Markets and Investor Relations Director. I joined the company in 2009. Prior to that I was head of Equity Sales at Benito y Monjardín and afterwards in Banco Espirito Santo. I started my career in derivatives, as a market making, and also prior to joining the company I was working at a local asset management firm in Spain, Solventis, where we also provided consulting to hedge funds. One of the things I did, in my prior post before I joined the company, was the listing Zeltia in 1999, in 1998 in marketing and sales. It was my first contact with the company.
Besman: Joe good morning to you. Pascal Besman, I joined the company about four months ago after 34 years on Wall Street as a healthcare institutional salesperson.

Slingshot: Pascal, you and I have known each other from back when I was on the buy-side at SAC ,and for years, so it's great to be working with you once again on this and doing a call.
I know we have a lot of different levels of familiarity with the PharmaMar story on the line right now, and I think it could be really helpful if we just got a minute or two on the history, and how your products have come about. I know that there's an interesting story that unifies them, so maybe if you guys could walk me through how the company's gotten to where it is today.
Luis: PharmaMar was founded in the late '80s. The vision, the idea of our chairman, who was the founder of PharmaMar, he had this idea about developing drugs from the sea. He's a full biochemistry professor, so he's a scientist himself, and he had this idea that searching in the sea could be a very good source of raw materials to develop drugs. Most of the drugs came from land, so he thought there could be very good opportunities to search in the sea. And at the time he had the opportunity of searching the sea, because he had access to boats from different companies, and he had an opportunity, so that's how we started. That's the origin of the company. That was the idea of our Chairman.
Throughout the years, it's proven a successful idea. YONDELIS® is a clear example of that. It's a molecule that was discovered from a marine invertebrate, from a tunicate. It's reached the market. Throughout the years, we've also built up what is probably the biggest marine library of samples in the world. We have over 200,000 different samples, which are perfectly classified the specificity of all of them. Also the fact that we search in the sea; we only get inspired in by the sea. We only have a few grams of invertebrates, and then we have to synthesize them in the lab.
That also has proven for us - in a sense that has allowed us to develop drugs within a novel mechanism of action. Not only just because of the sea, but what this has proved is that we came up with the novel mechanism of action, that could find a niche in the market, or some of them have proved to be very synergistic with the current drugs being developed. So far the model has worked very well for us, and we're leaders and we're pioneers in searching the sea to develop drugs.

Slingshot: To understand what you're saying there, the inspiration or the knowledge for the molecule comes from the sea, but you guys then synthesize it in the lab and don't actually rely on a marine source for the production of the drug.
Luis: Exactly. Yeah, we just need a few grams as an example to get inspired, and then as you just pointed out we synthesize that in the lab. Unless we are able to synthesize a molecule, and we've seen [inaudible 00:08:10]; if we're not able to synthesize, it's not feasible to develop that. So that will be a red flag to stop it.

Slingshot: Got it. Excellent. I understand that. What things have you gotten from the sea? Can we talk through the key assets of PharmaMar?
Besman: Yeah thanks Joe.

Slingshot: Some people are on the line, I know, have said they're not quite familiar with you guys, and they're excited to learn, so just ... What do you guys see as your major assets? I know YONDELIS® is approved,

Resultado de imagen de pascal besmanBesman: YONDELIS® is our first drug, and it's approved in over 80 countries in the world, something a lot of bio techs can't say. It's approved in Europe for sarcoma and ovarian, in the US we have a partner, Johnson & Johnson, and in Japan, Otsuka through Taiho, which both got only the sarcoma label so far, in the end of 2015. YONDELIS® did last year over $160 million of global revenues, of which we booked about a hundred of it, and it continues to grow and form the basis of a pretty good backbone to the corporation, given the revenue base.
We have an analog of YONDELIS®, a new and improved version shall we say, which is Lurbinectedin. You can call it 'Lurbi', if you want. And Lurbi is in two, soon to be three and four, pivotal Phase 3 trials. The first two indications are in ovarian, which is fully enrolled, with data due to readout second half of the year. Small cell lung cancer, second line is currently recruiting, and we've already stated that we are going to be going into a BRCA2 pivotal trial in due course.
Beyond those two, our marine discovery engine, which José Luis was just talking about, provides really a very rich pipeline of compounds to continue to push through development that we think in some ways is perhaps an eternal source of our pipeline.

Slingshot: That's interesting. Do you think that those compounds will be limited to oncology, and are you aware of any other companies with the synthesizing capability that you guys have been working on? Do you think it's only going to be limited to oncology applications, based on your early findings?
Besman: There's no intuitive reason to believe that mother nature decided to only put oncology drugs in the sea, so we intuitively would believe that there would be applications in infectives or CNS or Cardio, but that will not be something we do.
We are currently investigating business development to license access to the library for people who wish to prosecute it in other areas, but we're exclusively focused in oncology. As for synthesis, it's a very simple word and a very complex process. YONDELIS® itself is 18 steps to synthesize it, so it's not easy. I can't really say who or what has the capability. It's not necessarily totally unique, on the other hand it's not something that you can fall off a log and synthesize one of these compounds.

Slingshot: I think, when I was talking to various members about this call today, one of the most common questions was around Pascal's joining, and I wanted to ask Luis, what got you guys to bring Pascal onboard and to work on a US presence right now, given the stage of the company? I'd just like to hear how that got started, and what the process was like, and what the decision-making philosophy was?
Mora: We announced the strategy for PharmaMar to build the commercial operations in the USA for Lurbinectedin, because it is our key drug. So you know we sell a drug in Europe currently. We have a partners for the other countries, for YONDELIS®, but with 1183, we decided to move to the USA in order to sell directly. This is an important part of the strategy for the company. The other one is we want to win visibility in the USA to engage more consumers, patients, et cetera. When we searched the market, we were looking for the right person to help us to conduct this important study. In Pascal, we thought it was a good decision to incorporate Pascal into our team in order to lead the PharmaMar US strategy. We are very happy to have Pascal with us.
Luis: It may be interesting if Pascal could just give a hint about what your plans are in terms of gaining more visibility with patients and patient associations and trials.
Besman: Yeah. Thank you, Jose Luis. Certainly in the United States market, patient advocacy is very advanced, especially in certain cancers. And in those areas, we are already at relatively advanced stages of negotiating some partnerships that will help us really educate both patients, caregivers and the KOL communities, and really try improve enrollment curves, obviously, and really get the word out.
We're also going to be quite active in various other sponsorships through year of some lesser-known medical meetings. We were a sponsor for example of TAT, Targeted Anticancer Therapies, which is in Paris this week. So there's going to be a much louder noise about us and a louder presence in various areas.

Slingshot: Pascal I understand that strategy, but also what attracted you to PharmaMar? I worked directly on Wall Street for seven years, and lasted that long. What after such a long career, really enticed you to pick PharmaMar of all these clients, and what made you make the jump?
Besman: Thanks. I've known the team here for about a decade, Joe, and I really have been amazed at what they've achieved. When you think about how many biotechs, how few of them actually ever get a drug on one market, let alone 80, that's a very good starting point. In addition, I was very impressed with their professional and personal integrity. The revenue base of YONDELIS® really is a tremendous foundation that very few biotechs, the binary bio techs, who you say that I was working with so many of them, have.
In addition, when I think of lurbinectedin compared to YONDELIS®, I think it's undeniable at this point that it's an active drug. So based on that and the law, the rule of multiplicity, I think the chances of it failing in four consecutive Phase 3s is pretty slim. And if that is going to be the case, that it will succeed at a minimum of one of the Phase 3s, and I think it may be more, then the valuation gap of PharmaMar, compared to what it would be if it was an American biotech, was just too appealing to pass up.

Slingshot: I think that's a great segue, because the biggest comment after the curiosity around your move, Pascal, has been around the listing status of you guys. Madrid isn't a gating factor for a lot people on the phone, but it is potentially a value-disconnecting one. Do you guys have any plans to list? I think I had seen on your Q1 call a mention about an F1, so can you just maybe give us an update, José or anyone, on what the times are for a US listing if there is one?

Resultado de imagen de jose luis moreno pharmamarLuis: When we announced the strategy a few years ago, the five year strategy, among those plans were potential listing or potential IPO in the US. That's the end of roadmap, and we getting the company ready. We haven't really mentioned our calendar or anything. We're just waiting for the right time to do it, in terms of market, price and the calendar of news flow for the company.
But it's a clear decision for us and a clear strategic decision. Going back about two, three years ago, when we decided on the strategy of focusing on oncology, and we set ourselves this goal of bringing two new drugs to the market, as well as YONDELIS®. So going from one compound to three compounds on the market, we had to put the structure of the company in line with the decision of focusing on oncology and making very clear that was our focus, and the rest was non-strategic.
That was one of the reasons why we did the reverse merger, allowing investors to invest directly in oncology. The second reason is whatever corporate movement we did, like an IPO or selling any non-strategic assets, the proceeds will go directly to the oncology company. Then getting the company ready to, as you pointed out, to make a step forward and go in the US. Yeah, there is no roadmap, certainly we cannot talk about our calendar at this point, but we've been working toward that, and when it is the right time from the market point of view, the price, we'll go ahead.

Slingshot: I wanted to talk about the pipeline, and I know that Lurbi is one of the more exciting programs. I think a lot of customers and members of Slingshot on this call, have been on PARP calls with us, whether they're specific to Tesaro or just the overall landscape and things like that. So when we hear about ovarian cancer as one of the first targets, I think a lot of people without doing any diligence, and myself included, think, "Oh, what about PARPs?" Could you maybe talk to us a little bit about the role in that landscape, how these things get approved, and how you guys fit.
Besman: This is a question we get in just about every investor meeting. So let's just remind everyone, you know, a PARP is a DNA repair inhibitor. As such, it kind of makes sense that it would be used after you've used a DNA damaging agent, whether it's a drug or it's radiation. That ties in very well with this new maintenance setting that we hear, which is after the usual platinum frontline therapy, which is a DNA damaging drug, and then you would use a maintenance, which is where olaparib is approved in EU and niraparib currently filed in the US and EU. Unfortunately, even with that maintenance setting, most women will then at some point progress, and be deemed, based on the time into that progression, as either sensitive, resistant or refractory.
Lurbi is seeking a label in ovarian resistance. YONDELIS® has a label in platinum-sensitive, and beyond that second-line setting, which is what we call sensitive resistant or refractory, comes the third-line setting, which is where we're seeing the PARPs again used. Again it intuitively makes sense after another DNA damaging agent, whether it's a rechallenge with a platinum or it's a Lurbinectedin, so that's where rucaparib got approved recently and olaparib is approved as well, in late line with mutation. Does that answer your question about the PARPs?

Slingshot: If I'm hearing you correctly, they're not competing in the same line of therapy, because they're approaching it differently mechanistically. So they complement each other more than directly compete for patients at the various points in their treatment cycle?
Besman: Yeah, that's correct. The PARPs are maintenance and third-line, and both the YONDELIS® and Lurbinectedin are in second-line.

Slingshot: Got it. So the ovarian trials coming up first this year, could you kind of give us a little bit of color on when in the year you think that those trials might read out? I have a few questions on the powering of the study, but ovarian cancer is fairly heterogeneous to the patient population, so when you think about those types of studies, their heterogeneity is one of the scary things for investors. So how do you guys power that, and how do you think about that, and what kind of comfort can you give us, given that backdrop?
Mora: Usually the ovarian cancer population is divided in three types of patients, the refractory to the third line, resistant, and sensitive. YONDELIS® is approved in ovarian sensitive, platinum sensitive. Our trial with Lurbi is for patients resistant to platinum, then this is the setting when we can do the trial.
The trial, we already have finished the recruitment. We included 443 patients in two arms; one is Lurbinectedin and the other arm is the investigator's choice of Doxil or Topotecan. The primary endpoint of progression free survival is powered at 90% of the hazard ratio 0.7. Then we expect to win in PFS very close to 30% in the control arm. We expect top-line results in the last quarter of this year, and we are confident that success in the Phase 2 trial will be the base to design and agree to a Phase 3 trial. The recruitment was very fast, faster than our expectations, then this will demonstrate that there is a huge medical need, and the second one is getting Lurbinectedin direct to the doctors. [missing audio 00:23:26]

Slingshot: The other thing that I noticed, the difference between the Phase 2 and the Phase 3, was the dosing of Topotecan, Topo. I think it was underdosed in the Phase 2, and I'd like to just understand how that came to be, why it was underdosed in the Phase 2? And then with the Phase 3 being daily, how have you guys, again back to the powering and thinking about that, how have you incorporated it?
Besman: That's a good question. So the Phase 2s happened during the period that the Doxil shortage emerged, and therefore the control arm had to be changed from Doxil to Topotecan. Topotecan is not a terribly easy drug to tolerate, and in this Phase 2 trial, while it was determined that the control arm would be an also quite often used Topotecan regime, which is weekly as opposed to daily, and the results for that are usually lessor, although it's more tolerable. And so the PFS that you see in our Phase 2s, of 1.7 months and the OS of 8.3 months are both, we acknowledge, lower than you would get with a daily Topotecan, which is part of our control arm in the Phase 3, the other part being the Doxil, which is no longer on shortage.
When you look in the literature at how Doxil and Topotecan have done in this population, it seems to be relatively constant in the highish two to lowish three months, and most seem to congeal around three months for Topotecan, 3.2 for Doxil. So the way we think about this is, if you take the highest that you get in this population, usually with Doxil, that would be about 3.2 months. To generate a hazard ratio of 0.7, back of the envelope math would say that's about a 50% improvement, 3.2 times 150% would see the drug arm need to be around 4.8 months, and that's about a 20% decrement to what we saw in the drug arm in the Phase 2. So we think that the trial is adequately powered to pick up the benefit that we expect to deliver, and the trial is stratified, so that we will have meaningful numbers of both Topotecan and Doxil.
Slingshot: So when you say 20% decrement, you mean basically that there's a 20% cushion based on the Phase 2 results to hit the powering in the study.[crosstalk 00:26:08]
Besman: I said we would need to be 50% better than 3.2 is 4.8, and we showed 5.7 months PFS.

Slingshot: Got it. So it's a pretty good cushion. Okay. Let me go on over to the BRCA2 trial, how are you guys thinking about enrollment there, and does the existence of PARPs and other PARP treatment out there, how much does that cloud the patient population? Does it make it harder to find them, or are those patients further down the line? How do you guys think about enrolling a trial like that right now?
Besman: Also a question that's asked quite a bit. The data that we presented at ESMO last year saw the objective response rate in the breast cancer, BRCA2, was 67%, 61% which was really eye-popping because most of the data we've seen so far has only been in BRCA per se. We know that BRCA2 is a tougher diagnosis than BRCA1, and we know that the PARPs have delivered objective response rates of the order of 25ish to maybe 30% in BRCA. So the 60-odd percent response rate was really eye opening, and with that in our pocket, we have met with the FDA and are finalizing a protocol that would see a single arm trial of 110-odd patients, with a single arm and an objective response rate endpoint.
So to your point about how easy or hard will it be to enroll this trial; it's hard to really give an answer, because no one's done it. That said, there's probably a population in the United States of about 7,500 women who meet our enrollment criteria, which would also have no prior PARP, and about 50% more than that, about 11,000 in Europe.
So we do recognize, it's likely to be challenging and for that we have already signed contracts with two leading patient groups, with a view to them helping us pick investigators, pick sites, educate their women, help get the word out that a trial is open, that it's a targeted therapy for BRCA2. And they're very enthusiastic about helping their members and working with us collaboratively, and we will be able to use their names publicly, so that people know that we are working with them.
So we're quite excited about that, and in addition, we're planning on opening an expanded access parallel trial to this, so that any woman who is BRCA2, who is ineligible, because she's had prior PARP, for example, will still be able to get Lurbi. We think that that really is something that will resonate with the patients advocates and the KOLs.

Slingshot: Yeah so that's interesting. I'm not as familiar with that, and you had mentioned it to me recently. Maybe if you could just talk a little bit about that. Is that any pharmaceutical company can make that decision or does the FDA approve it? It sounds a little bit like "right to try" to me that I hear thrown around a lot from the current administration in the US. How exactly does that program work? Maybe just a little bit ... That does sound like it could be interesting.
Besman: It's not "right to try" because the FDA is involved in allowing you to do this. If we go back a couple of years ago, there was an unfortunate situation with another public biotech that had a Phase 3 asset in CMV. A child had CMV and wanted to get access to the drug, and the company stated that they did not have a pediatric arm to put the child in. It became very much a viral news story, social media story, and ended up, unfortunately, costing the CEO his job. And to cut a long story short, the boy got the drug, the boy got cured, thankfully, the Phase 3 failed, and we'd like to avoid that situation happening to us.
So we've already spoken to the FDA, and we would like to have an expanded access trial on the side, here, and that will allow BRCA2 women who don't meet the eligibility criteria to enter, and they can be treated. It will help us collect a larger safety database. It will help us do analytics in terms of other subsets that may work, sequencing compared to PARPs, before/after/during. In addition, probably most importantly, it's the right thing to do.

Slingshot: I think that's pretty interesting. Okay. The third trial here, currently is small cell, and there's a change in the dosing in primary endpoint from Phase 3 to Phase 3. Could you just talk to us a little bit about why that was done, and what was done for progression free survival powering given this change? Again, just trying to understand these small but potentially important differences.
Mora: Yeah sure. This is an important change in the Phase 3, but I think it's in favor of the patients and in favor of the trial. In the Phase 2, we use a flat dose, seven milligrams per square- seven millimeters flat. We analyzed all of the patients, and the equivalent, because seven milliliters flat dose is the actual dose in the trial by a square measure. Then, this is personalized more to the dosing in the patient and not to the activity. Then we reduced dramatically the secondary effects we observe in the Phase 2, but non detrimental objectivity.
And then the second point is, we met with authorities, with the FDA, and the response rate is important but in small cell lung cancer, they consider it is an approval endpoint of PFS. We have extremely good PFS in Phase 2. We have achieved 4.6 months if you consider our resistant and sensitive patients in this Phase 2. Then if we consider only the sensitive, we never disclose, but you can suppose it is much higher than this 4.6. If you compare this 4.6 with the historical data for Topotecan, nivolumab, pembro, Rova-T, they are smaller numbers than our PFS. We designed the trial and powered it for progression free survival, primary endpoint, and overall survival as a secondary endpoint. The trial was agreed to by the FDA, and Pascal mentioned before is well underway.

Slingshot: Great. On the business development side, I saw the press release with the deal in Japan, and it seemed to kind of go under the radar just looking at the stock and some of the things that I watch, in terms of analysts and things. I wanted to just get a sense on what you guys thought of that business development deal. I have a technical questions, actually from another member, but what kind of structure partnerships are you looking for, going forward, for Lurbi? Is Japan a one off in terms of partnering, or ... I'm trying to get a better sense of the structure you guys have in mind, for how you want to bring Lurbi to market, considering how much of the economics you own currently. And whether we should think of Japan as indicative, or just a one off, a nice cash deal?

Resultado de imagen de pharmamar pipelineBesman: I'll answer the first portion, and José Luis will answer the second. In terms of how we think of the deal and what the market thinks of it, we were fortunate to sign the deal December 22nd, and we were unfortunate to sign the deal December 22nd because obviously many people were already on their holidays. But it is what it is, and we were happy to cash the check regardless of the day the deal was signed.
Japan represents approximately 10% of the world's oncology market, so I think most people can do the math and work out what Chugai, which is part [missing audio 00:34:42], and what the asset was worth, and that probably means a lot more than what we think it's worth. We're delighted to have Chugai, which is the leading oncology player in japan, as our partner. And in terms of other business development, and what our plans are for Lurbi, I'm gonna let José Luis answer that one.
Luis: We have a very clear idea about our intention in the US for instance, as compared to YONDELIS®. Luis mentioned before, our idea is to keep commercial rights in the US, so therefore, set up our own sales force, and sell direct. We could either do it on our own, or obviously since we started showing Lurbi's data, we've been approached by different companies and stuff and conversations. So we had a good deal, and what we can say is something very good. We also are contemplating co-promotion agreements. There's early conversations for that, and that's our idea.
We reached the this point where we are releasing data on Lurbinectedin, two in Phase 3, perhaps another one starting shortly, so we're very confident about comparing the drugs, and we have experience of building up YONDELIS® in Europe, which has been successful. We have a very successful sales force, and believe me, building up a sales force in Europe is a complete nightmare. I mean you have to go country to country, you've got 27 languages, all different regulations, then once you get the approval, you have to get the reimbursement in every single country. Even in countries like Italy or Spain, it's not even a single country, it's every single region, which is a nightmare. And we succeeded. Not that many companies have reimbursement in almost all countries in Europe, in sarcoma, including positive recommendation from the NICE in the UK.
I think we gathered all that experience, and in the US, it's more straightforward. It's one country, one language, and all the reimbursement with insurance companies is much more straightforward than it is in Europe.

Slingshot: I spent a lot of time following the Intermune pirfenidone launch when that became the key story going through Europe, and it was pretty incredible to watch how many years and how managerially challenging that was compared to a US launch when you turn on a switch. So that's an interesting background view to be coming at this from.
One question technically, just on the Japanese deal, in terms of the way you guys counted the money, was it 30 million up front, but I think only 6 million went in in 2016, so is the other 24 going in, or are we reading that wrong? That was submitted from somebody listening.
Luis: I mean, that's pretty clear and very straightforward. With the new IFRS that is implemented, in regard to all these type of agreements, we need to recognize or account in our accounts the amount that is linked to all the commitments we have throughout the agreement. That means, we only accounted for 6 million in 2016, and the rest, 24, will probably be recognized within the next couple of days.
As Pascal said, we were lucky enough to sign that in December '16, but the good thing, which is more important for us, is that the cash was in-house, and we cashed the 30 million just a few weeks after. So it was the first half of January, when we got the 30 million, and that was a very important grant. Because yes, in terms of the accountants, and obviously the P&L did not reflect the 30 million, but from the cash position point of view, if we take the 33 million that we released for the year 2016, and we add 30 million, we have a total of 63 million that would have been proforma as of December, and is what we can really have. And that, given our burn rate, that we released of 8.4 million is clearly a very comfortable position for us, at least the next few years to get to our goals that we set ourselves- as we mentioned before of getting the next two compounds on the market.
From that point of view we're very comfortable with our capital and cash structure, and that allow us to concentrate, basically, on our trials and not to worry about the cash.

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Slingshot: Great. I think you already answered, also for anyone listening on the line right now, we're through the questions that I mapped out, which a lot of that was from input of other people listening, but I'm onto the section of things that have been submitted mostly during this call on the project page, so if anybody still has a question, I'll ask that right now. Just for anybody new to these types of calls.
I think that one of the questions that came in, you just answered in terms of your expansion plans in the US, but there is sometimes a nuance with US pharma companies between co-promote and go alone, and so I wanted to see if you guys did have any intentions or considerations around co-promotion in the US for Lurbi, and if they are, I guess they want to know how advanced they are, but I'd be surprised if you want to answer that.
Besman: It's a question we get asked. Obviously, it's nice to have a beautiful daughter that people want to marry. We intend at this point to hang onto Lurbinectedin rights in the United States and build a commercial infrastructure around that. And as Jose Luis said, we think that given our experience of doing this with the complexities in Europe, that we can do this.
On the other hand, we are also very willing to talk to people, who think that our daughter is as beautiful as we think she is provided they have a nice, big dowery, we're willing to talk. But this is our daughter, and we care very much about our daughter.
The other thing that I would say, which is perhaps the flip-side of this, is that the sales force that we've built up over the years in Europe, is a truly strategic asset that we think can be leveraged with other companies who may have a European oncology asset that may not have enough peak sales to justify the critical mass required to have that same infrastructure, and so there's an opportunity there for us to leverage that existing sales force.

Slingshot: Another question here: Are you guys giving any update on the progress of the EMA review for Aplidin? I remember, again, back to the pirfenidone days, kind of going in and asking, "Have the minutes come? Have you guys presented? Where does that stand?" So I don't know if you guys are commenting on that. I don't think that's that common, but is there any update on the progress there?
Mora: Aplidin is in the regulatory process. We submitted the dossier last year. The dossier enclosed the ADMYRE trial, the trials in multiple myeloma, three prior lines. The trial was agreed with EMA, and the trial we announced was a positive trial. Then the regulatory process in Europe is dead, it's in an orphan status, and multiple myeloma is longer than in the USA, unfortunately, and can take about one year. Then we expected the CTMP opinion in the last quarter of this year. So today is in the normal regulatory process, the question and answer from the authorities, and that's it, when we have that, when we have the decision by the CHMP we will announce, and we expect that to be in the last quarter of this year.
The multiple myeloma is an interesting market in this line because there's not many drugs that are approved with three prior lines. Aplidin is a unique mechanism of action, completely different to the other drugs as a protozoan inhibitor. It is not like the lenalidomide families; it's a target therapy. We described it in Nature, last year, and it's safety profile is very good, and can combine with the other drugs.
The market in the three prior lines in Europe is growing after some approval in Europe, and we are working with with Chugai- we have a deal with Chugai Pharma for co-promoting to some countries in Europe.

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Slingshot: Here's another one that came in that's interesting to me a little bit: Pascal what's kind of the biggest surprise you've had going over to PharmaMar, and maybe your biggest frustration switching to the corporate side, after so many years on Wall Street? What have the first few months been like for you?
Besman: I've enjoyed it very much. I guess the biggest surprise has perhaps also been my biggest frustration, is that there persists to be quite a number of Real Madrid supporters here. I just don't understand it. None in the room, I hasten to add.
I think that the biggest surprise here has been the absolute willingness to accept change, and not have "not invented here syndrome". I find it really remarkable that they are very very open to listening to ideas. For example, patient advocacy, as you may well know, in Europe, especially in southern Europe, is just not even in its infancy yet. It's not even in utero, shall we say. Whereas in the United States, it's incredibly well organized. I think it's quite a feather in our collective caps that in the four months since I've been here, we've embraced the change to do this, and we've already signed two contracts. So that would be something that has really surprised me.

Slingshot: I think there's just one question here, around burn rate, and they quoted a number, but maybe of you guys could just talk about the company burn rate. I know it's in some of the slides, but you know, what it was for 2016, and if you guided it all around '17, but maybe just help to clear up exactly where you guys are in a cash position.
Luis: We don't do guidance for 2017. Burn rate at our operating level last year was at 8.4 million, and that meant -all that taken into account 30% increase in R&D investment. So last year in oncology was 78 million. One thing we can say was that this year the R&D investment is not gonna grow at the same rate. We're talking about single or lower double digits, so it's not, definitely not growing at the same rate. We spent revenue from YONDELIS® carry on growing at single digits, so from that point of view ... Now burn, we have zero guidance, but should not change that much, and as we mentioned, with the cash that we have already, we have for the next few years a pretty comfortable position.
As for the debt that we have, also we think we're moving the debt pretty nicely. It was a little below 20 million that we refinanced this year, to term debt. By the time we start our [inaudible 00:47:48] 20 million that we need to give back and we've been renewing that pretty nicely, so it's not a problem either.

Slingshot: I think we're coming up on the time here for the call, and I've gotten through most of the questions on the site. Maybe we can just wrap up with any key takeaways that you have and the biggest catalyst coming up on 2017.
A lot of Slingshot members will know how we do our best to organize and structure catalyst events for every stock that we have, in order to give people an idea of when value creation events are going to happen. So some of those are on the project page associated with this, but if you wanted to walk through what you guys see as the most important and exciting catalysts through the rest of this year that could be a good way to end this.
Besman: Sure, so let's just do these, rather than chronologically, by importance, and certainly the most important read this year, catalyst this year, will be the Lurbinectedin Phase 3 data in ovarian cancer, which we anticipate in fourth quarter. It's by the way, not just an event driven in terms of the timing, when one compares to when the last patient's last visit was, because we are also looking to deliver a significant OS dataset to support the application. So it will be quite more mature than you would think in terms of OS.
We also, in probably the fourth quarter, will get the answer from EMA, we think, on the Aplidin application. And probably around the middle of the year, in small cell you'll get a couple of things of interest. You'll get an interim look, which is a futility look only, and in addition we should, at one of the mid-year-ish medical meetings, have some further supportive data of Lurbinectedin in small cell. And then lastly, at some point during the year, we can't really control timetable totally, we should give an update and hopefully have started the breast cancer trial. Those are the main ones for this year.

Slingshot: Great. That's all the questions I have and that I see coming in. Again thank you very much. I know you're very busy, and I appreciate the time to come on and talk to both myself and our community. It's pretty neat to have this kind of access, directly to an exciting story, and so I think the next things that that we have talked about are potentially our KOL call, which is something that the members of Slingshot are a little bit more familiar with, but maybe digging into some of the Lurbi data, ovarian and other diseases. So, we'll be back reaching out to people with that. But in the meantime, I just want to thank you very much again for taking the time. This was great.

Besman: Thank you, Joe. Thanks, listeners. We enjoyed doing it.
Luis: Thank you.
Mora: Thank you very much.
Slingshot: Perfect. Thank you, guys. Have a great afternoon.