Oryzon nomina un inhibidor de LSD1 como candidato preclínico para el tratamiento de la Leucemia Aguda

ORYZON ha decidido entrar en desarrollo preclínico con su segundo fármaco candidato, un inhibidor específico, primero en su género, contra la Lisina Especifica Demetilasa 1 (LSD1) para el tratamiento de la Leucemia Aguda y otros cánceres hematológicos La inhibición de LSD1 reduce la carga tumoral especialmente modelos de leucemia atacando las células totipotentes cancerosas sin afectar a las células progenitoras mieloides normales.

La leucemia aguda mieloide (LMA), se tratan todavía con versiones mejoradas de viejos fármacos desarrollados hace 40 años. Desgraciadamente, la quimioterapia intensiva y el trasplante de medula ósea curan solo en un 50% de los casos. Hay un fuerte consenso entre hematólogos y oncólogos de que existe una gran necesidad médica de nuevos fármacos para estos pacientes, La inhibición de LSD1 es una aproximación innovadora para detener esta enfermedad que podría ayudar a resolver esta necesidad clínica.

Los científicos de Oryzon han mostrado en modelos animales que la inhibición de LSD1 podría ser eficaz en el tratamiento de leucemia linfoblástica aguda (ALL) que representa un 25% de la leucemias juveniles y en ciertos tipos de mieloma múltiple y leucemia linfocitica crónica. Además, en estudios independientes, los inhibidores específicos de LSD1 de ORYZON han mostrado ser eficaces en el tratamiento de la leucemia mieloide aguda (AML), que representa el 40% de todas las leucemias del mundo occidental, y especialmente de las que presentan ciertas reordenaciones moleculares (conocidas como sub-tipo MLL debido a la implicación del gen MLL).

El candidato escogido por Oryzon es un inhibidor de LSD1 enantioméricamente puro, potente y selectivo, de bajo peso molecular, con características farmacológicas excelentes y activo in vivo a muy bajas dosis de hasta 0.05mpk. El candidato es biodisponible oralmente con buena PK, y un muy buen perfil de seguridad y selectividad. Tras la fase de seguridad toxicológica regulatoria que finalizará a finales de 2012, la compañía espera poder probar su eficacia en pacientes humanos en Fase I/IIa a principios del próximo año.

La próxima semana Oryzon presentará los últimos avances de su programa farmacéutico en LSD1 en cánceres hematológicos en la 2ª Conferencia GTC’s en Epigenetica y Drug Discovery dentro de la sesión Drug Discovery in Epigenetics: el 30 de mayo en el Hyatt Harborside de Boston. En esta conferencia internacional presentarán sus avances en el campo otras compañías como Novartis, GSK, Pfizer y Genentech

Tras 4 años de esfuerzo en nuestro programa de descubrimiento de fármacos inhibidores de LSD1 hemos producido casi 800 compuestos. Ahora nuestros resultados y los de otros muestran que hay un subconjunto de cánceres hematológicos en los que la inhibición de LSD1 configura un mecanismo de acción particularmente eficiente. Hemos constatado que existe un elevado interés entre los hematólogos y los oncólogos por esta nueva aproximación. Estamos realmente impacientes por comprobar el potencial de estos compuestos en la práctica clínica.

Oryzon nominates LSD1 inhibitor as preclinical candidate for Treatment of Acute Leukemia

ORYZON is proceeding in preclinical development with its second drug candidate, a first-in-class specific Lysine Specific Demethylase 1 (LSD1) inhibitor for the treatment of Acute leukemia and other hematological cancers hematological cancers. Our LSD1 inhibitors reduced tumor load especially in acute leukemia models by targeting Leukemia Stem Cells, while normal myeloid progenitor cells were spared.

Acute myeloid leukemia (AML) are still being treated today with updated versions of old drugs developed 40 years ago. These intensive chemotherapies and bone marrow transplantation provide successful therapy in only 50% of the cases. There is strong consensus among hematologists and oncologists that there’s an urgent need for new drugs. Inhibition of LSD1 is a completely new approach to halt this disease and could help to address this medical need.

ORYZON’s LSD1 advanced leads were efficacious in the treatment of Acute Lymphoblastic Leukemia (ALLs), which represents 25% of juvenile leukemia, and in certain types of multiple myeloma and Chronic Lymphocytic leukemia. Independently, Oryzon´s compounds were shown to be efficient in the treatment of acute myeloid leukemia (AML), which represents 40% of all leukemia in humans, and especially in mixed lineage leukemia (MLL), an aggressive form of acute myeloid leukemia. These data that were published recently in CancerCELL by a UK research team, indicate that there is a significant potential therapeutic window for the use of LSD1 inhibitors in the MLL molecular subtype of AMLs.

Oryzon’s drug candidate is a enantiomerically pure, potent and selective compound with a low MW, good pharmacological properties, orally bioavailable, with good PK, safety and selectivity profile. Our candidate is active in vivo at doses of down to 0.05mpk. After successful completion of regulatory toxicology studies, we expects to move quickly the compound into Clinical Phase I/IIa early next year.

Next week, Oryzon will present its LSD1 program in Acute Leukemias at the GTC’s 2nd Epigenetics in Drug Discovery conference in the session Drug Discovery in Epigenetics (May 30-31 at the Hyatt Harborside in Boston, MA). Other pharmaceutical companies as Novartis, Genentech, Pfizer or GSK among others will participate.

We have been working really hard the last 4 years in a first in class drug discovery program in LSD1 inhibition, producing almost 800 compounds. Now, we and other scientists have identified a subset of hematological cancers in which LSD1 inhibition defines a mechanism of action that looks particularly efficient. We have also verified the high interest amongst hematologists and oncologist for this new approach. We are really eager to see the potential of these compounds in the clinic.

Oryzon presentará sus avances en Leucemias Agudas en la 2ª Conferencia GTC’s en Epigenetica y Drug Discovery en Boston

Nuestra Directora Científica, Dra. Tamara Maes, viaja a Boston donde, presentará los últimos avances del programa farmacéutico de ORYZON en LSD1 en cánceres hematológicos en la sesión Drug Discovery in Epigenetics: el 30 de mayo en el Hyatt Harborside de Boston.

La presentación de la Dra. Tamara Maes tendrá lugar el 30 de mayo a las 16,45 con el título “Desarrollo de nuevos y potentes inhibidores de LSD1 para el tratamiento de tumores hematológicos”. Moléculas inhibidoras de LSD1 han demostrado ser eficaces en el tratamiento de determinados tipos de leucemias agudas según estudios preclínicos publicados por grupos científicos independientes del Reino Unido, en las revistas Nature Medicine y Cancer Cell. Las moléculas desarrolladas por Oryzon, han demostrado ser eficaces en el tratamiento de la leucemia mieloide aguda (AML), que representa el 40% de todas las leucemias del mundo occidental, y especialmente de las que presentan ciertas reordenaciones moleculares (conocidas como sub-tipo MLL debido a la implicación del gen MLL). Los científicos de Oryzon han mostrado además que la inhibición de LSD1 puede ser eficaz en el tratamiento de leucemia linfoblástica aguda (ALL) que representa un 25% de la leucemias juveniles y en ciertos tipos de mieloma múltiple y leucemia linfocitica crónica.

La 2ª Conferencia GTC’s en Epigenética y Drug Discovery en Boston reúne a una mezcla de expertos de la Industria y la Academia y tendrá como conferenciantes destacados entre otros al Premio Nobel Dr. Craig C Mello, que hablará sobre RNAi e inmortalidad. La sesión Drug Discovery in Epigenetics será moderada por el Dr Quamrul Hassan, de Los Institutos de investigación Biomédica de Novartis y dará una visón de las tendencias actuales para modular dianas Epigenéticas. En la misma sesión que la Dra. Maes hablarán el Dr. Rab Prinjha Vice Presidente y Director de Epinova Epigenetics DPU (GlaxoSmithKline), el Dr. Arthur M. Krieg Directors de RaNA Therapeutics y el Dr.Claes Wahlestedt, Decano para la Innovación Terapéutica en la Universidad de Miami . En otras sesiones participaran otras compañías relevantes como Genentech o Pfizer entre otras.

La epigenética es un área candente en la industria farmacéutica; se predice que los ingresos globales para las terapias y las tecnologías epigenéticas alcanzarán $2.73bn en 2015 y que el mercado total crecerá con un CAGR (tasa anual compuesta de crecimiento) del 16% entre 2010 y 2015. Las terapias seguirán siendo la mayor fuente de rédito en el mercado de la epigenética. Asimismo, la actividad de partenariado y de acuerdos en este ámbito es intensa.

Oryzon presents its LSD1 program in Acute Leukemias at the GTC’s 2nd Epigenetics in Drug Discovery conference in Boston

Our Chief Scientific Officer, Dr. Tamara Maes travels next week to Boston.  She will present the latest advances of our LSD1 program in hematological malignancies at GTC’s 2nd Epigenetics in Drug Discovery conference in the session Drug Discovery in Epigenetics: on May 30-31 at the Hyatt Harborside in Boston, MA.

Dr. Maes' presentation will take place on May 30th at 16:45 pm under the title “Strong and specific LSD1 inhibitors for treatment of hematological malignancies”. Drugs against LSD1 have been shown to be effective in the treatment of acute leukemia. These preclinical findings have been reported by two British independent groups in recent issues of Nature Medicine and Cancer Cell.

The GTC’s 2nd Epigenetics in Drug Discovery conference brings together a mix of leading experts from the industry and academia and will have preeminent speakers as Dr. Craig C Mello, Nobel Laureate, who will talk about RNAi and Immortality.  The Drug Discovery in Epigenetics session will be chaired by Dr Quamrul Hassan, of Novartis Institutes for BioMedical Research, who will give an overview of current trends to modulate Epigenetic Targets. In the same session, Dr. Rab Prinjha Vice President, Head of Epinova Epigenetics DPU (GlaxoSmithKline), Dr. Arthur M. Krieg Chief Executive Officer of RaNA Therapeutics and Dr.Claes Wahlestedt, Dean for Therapeutic Innovation from University of Miami Miller School of Medicine, will also present interesting aspects of the field. Other companies as Genentech and Pfizer will participate in other sessions.

Epigenetics is a hot spot field in the pharmaceutical industry. It is predicted that world revenues for epigenetic therapies and technologies will reach $2.73bn in 2015 and that the overall market will grow with a CAGR of 16% between 2010 and 2015. Therapies will remain the largest source of revenue in the epigenetics market. The deal activity on the field is intense.

LSD1 is a target in Acute Myeloid Leukemia

In the last two weeks two critical papers have been published in Nature Medicine and in Cancer CELL pointing out the role of LSD1 as a pharmacological target to treat certain leukemias. In the CELL paper, the team from the Cancer Research UK Leukaemia, directed by Tim Somervaille used a mouse model  of human MLL- AF9   leukemia, and identified the lysine - specific demethylase LSD1 as an essential regulator of leukemia stem cell potential.  In a subset of Acute Myeloblastic Leukemias, known as  MLL- AF9 for the occurring molecular mutations, LSD1 is a key effector which  may   be selectively  targeted to produce therapeutic effect. Their data  point to a significant potential therapeutic window for the use of LSD1 inhibitors in the MLL molecular subtype of AML.  In the experiments reported in this paper Somervaille’s team was using LSD1 inhibitors described in Oryzon’s patents. In the Nature’s paper, the lead team of the Division of Molecular Pathology, Institute of Cancer Research, Sutton UK, directed by Anthony Zelent  in collaboration with other labs identify LSD1 as a therapeutic target and for AML pathogenesis and show that the combination of LSD1 inhibition with treatment with all-trans retinoic acid greatly enhance the therapeutic response.

One of the needs for any drug is to find those diseases or subset of diseases where the mechanism is more efficient. It has been proven now that certain leukemias are the first target for LSD1 inhibitors. However, due to its high level expression, LSD1 has been suggested also as a therapeutic target in other types of cancer as  poor- risk  prostate adenocarcinoma  ( Kahl et al., 2006), poorly differentiated neuroblastoma (Schulte et al., 2009) and high grade ER negative breast cancer  (Lim et al., 2010).

Oryzon has been producing in the last years almost 800 different compounds that are extremely potent (in the low nanomolar range) and with excellent pharmacological properties. We have also seen significant tumor reduction in several animal models like acute lymphoblastic leukemia and breast cancer and our CSO, Dr. Tamara Maes was a few weeks ago presenting our program at the 4th  Annual CHI X-Gen Congress, in the CLINICAL GENOMICS.  Epigenetics,  Targets  and  Therapies in San Diego, California. This program is covered by a set of 20 patent applications giving us a dominant IP position in the field. We are confident that our molecules will have a role in the future in the therapies designed for these devastating diseases.

Bio-Europe 2012, figures and feelings from Amsterdam

A few days ago I attended Bio-Europe Spring. The spring was shining in Amsterdam and the city was beautiful and welcoming as always. The meeting was intense: 2,157 attendees from 1,304 companies participated in 11,172 one-to-one meetings and we could chose between 135 company presentations.

The industry atmosphere was showing clear signs of improvement and a few companies as Almirall were jubilant by the recent FDA approval of its aclidinium bromide for COPD Treatment. 26 companies and entities from Catalonia were there, making up 57% of the total Spanish representation at BES 2012.

Of special interest were the Opening Remarks by David Thomas that were covering three main topics: Public market performance in the US vs other sectors, Private funding environment and Drug pipeline deal volume (see here its slides). The public performance of the 300 public US biotech was in 2011 clearly outstanding with an averaged +12% compared with the -25% of the median of the rest of sectors. In the current year the trend is still better for biotechs and, more interesting for European eyes, the public investors are more focused on small early stage companies (53% of the investments were done on companies with less than 100M USD of MarketCap and 48% on companies on early stage). This should be a good couple of bullet points for those in Europe that are skeptic about the sector.

In the side of the Funding environment the more striking figure was the 32% forecast of increase of investment on orphan diseases, here the prospects of small companies to retain value is higher.
Finally, David presented the figures of deals with upfronts bigger than 10M USD before and after the crisis. The overall number has decreased from 165 in the period 2006-2007 to 114 in the 2010-2011, here I guess the mergers in the big companies could have play an additional role to the global economic slowdown. But, interestingly, if we analyze the data we see that the early deals (PC and Phase I) are still robust (24% in the period 2006-2007 for 25% in the 2010-2011). If we consider only the PC deals the average is 37% in both periods. So there is room, as always, for companies with early assets to get fruitful deals. It was a great meeting and it is a fantastic sector.

Biotech is still alive

As I said in the previous post, despite this gloomy hubris, Biotech is still alive. Some news are giving hints that some thawing is occurring in this never-ending postnuclear winter that the debt crisis brought to Europe nobody remembers how long ago… ok, taken, it is not a catharsis yet but still things are moving.

Thus just to mention some of them: Danish biopharma Symphogen has raised €100m in the largest ever funding round for a European biotech company. The private Danish biopharmaceutical company, is developing antibody therapeutics to treat cancer, with rozrolimupab (Sym001), for the treatment of Idiopathic Thrombocytopenic Purpura (ITP) and prevention of Hemolytic Disease in Newborns (HDN) starting Phase II.

French diabetes firm Adocia raised €25 million ($33 million) in the first European biopharma IPO of the year.

And for US companies or markets , Alnylam, the RNA interference based company raised $87 million through a public offering of 8.6 million shares. Ceptaris has raised $15 million in a venture debt financing to help fund its transition from a clinical-stage company to one that anticipates commercializing its first product later this year. Satori Pharmaceutical the firm devoted to Alzheimer’s disease announced that three existing investors would put up to $15 million in convertible debt as a bridge to the clinic for its disease-modifying drug. While the French orthopedic imaging firm EOS imaging went public on the NYSE Euronext February 15 and raised €38 million.

There is consensus in strategic analysts that biotechnology is not only the most important success factor in future economic development – it will also change the global power balance: “the one who controls the chips also controls the game”. Anyone travelling to Shanghai, Singapore and other Far East hubs agree that Asia is quickly catching up in the biotech space. So we better keep moving ahead.

In Spain, where we suffer from some lack of international visibility, some Funds specialized in biotech are being raised and there is hope that they will contribute to the consolidation and maturation of a sector with some very nice jewels yet to blossom...