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Data Monitoring Committee Recommends Continuation of APOLLO Phase 3 Clinical Trial of Patisiran for Hereditary ATTR Amyloidosis with Polyneuropathy (hATTR-PN)

On October 10, 2016 Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, reported that the Data Monitoring Committee (DMC) for the Phase 3 APOLLO study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN) met on October 7, 2016 and recommended continuation of the trial without modification (Press release, Alnylam, OCT 10, 2016, View Source;p=RssLanding&cat=news&id=2210373 [SID:SID1234515688]). The APOLLO DMC met at the request of the Company following the decision – announced on October 5, 2016 – to discontinue development of revusiran for the treatment of hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM). The DMC will continue to meet periodically per their remit to monitor the overall safety of patisiran in the APOLLO study through its completion.

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The APOLLO study has completed enrollment of 225 patients at 44 sites in 19 countries, between December 2013 and January 2016.

"As part of our vigilance around patient safety, we felt it was important to take immediate action and requested that the APOLLO DMC convene to evaluate accumulated safety data from the randomized, placebo-controlled Phase 3 study of patisiran," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer at Alnylam. "We’re pleased to learn of the DMC’s recommendation that dosing can continue in APOLLO, and we look forward to the top-line data readout from that study expected in mid-2017. There is substantial unmet need in hATTR-PN and we are committed to advancing patisiran through development in hopes of bringing a new and needed treatment option to patients."

About ATTR Amyloidosis

ATTR amyloidosis is a progressively debilitating and often fatal disease caused by deposition of transthyretin (TTR) in peripheral tissues. TTR protein is produced primarily in the liver and is normally a carrier of vitamin A. In hereditary ATTR amyloidosis (hATTR), mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. Hereditary ATTR amyloidosis represents a major unmet medical need with significant morbidity and mortality; hATTR amyloidosis with polyneuropathy (hATTR-PN) – also known as familial amyloidotic polyneuropathy (FAP) – affects approximately 10,000 people worldwide. hATTR-PN patients have a life expectancy of 5 to 15 years from symptom onset, and the only approved treatment options for early stage disease are liver transplantation and tafamidis (approved in Europe, certain countries in Latin America and Japan, where it is approved for all stages of disease). There is a significant need for novel therapeutics to treat patients with ATTR amyloidosis.

Sanofi Genzyme Alliance

In January 2014, Alnylam and Sanofi Genzyme, the specialty care global business unit of Sanofi, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. Alnylam retains product rights in North America and Western Europe, while Sanofi Genzyme obtained the right to access certain programs in Alnylam’s current and future Genetic Medicines pipeline in the rest of the world (ROW) through the end of 2019, together with certain broader co-development/co-commercialization rights and global rights for certain products. In the case of patisiran, Alnylam will advance the product in North America and Western Europe, while Sanofi Genzyme will advance the product in the ROW.

About RNAi

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About LNP Technology

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

OncoResponse Secures $7M in Supplemental Series A Funding

On October 10, 2016 OncoResponse, an immuno-oncology antibody discovery company, reported that it has raised $7 million in a supplemental Series A financing, consisting of a $3.5 million investment from GreatPoint Ventures and a $3.5 million investment from the Helsinn Investment Fund (Press release, OncoResponse, OCT 10, 2016, View Source [SID1234522898]).

In October 2015, OncoResponse secured $9.5 million as part of an initial closing of its Series A financing co-led by ARCH Venture Partners, Canaan Partners and MD Anderson, with William Marsh Rice University and Alexandria Real Estate Equities also participating. An additional $3 million investment by Baxalta (now Shire) in May 2016, along with the recent investments by GreatPoint and Helsinn, bring the total Series A financing to $19.5 million, which will be used to support OncoResponse’s ongoing efforts to interrogate the humoral response of elite responders to cancer immunotherapy to identify antibodies and potential targets for novel therapeutic development.

OncoResponse utilizes a clinically validated platform technology to rapidly screen antibodies made by the human immune system and identify those with exceptional reactivity to cancer immunotherapy. The company has an ongoing strategic alliance with the MD Anderson Cancer Center, which provides access to patient samples and oncology and translational medicine expertise including clinical and regulatory input.

"We are pleased to welcome GreatPoint and Helsinn Investment Fund to our solid team of investors," said Clifford J. Stocks, CEO of OncoResponse. "These additional funds will support the continued progression of our research programs that aim to identify therapeutically relevant antibodies from patients with elite response to cancer immunotherapy in a number of oncology indications."

"OncoResponse is using innovative technology to develop a deeper understanding of the immune response to cancer immunotherapy," said Andrew Perlman, Co-Founder and Managing Partner of GreatPoint Ventures. "At GreatPoint, we look for companies with uniquely advantaged approaches to solving frustrating problems, and OncoResponse’s pioneering approach to novel target and antibody discovery from elite responders is directly in line with our investment strategy."

"This investment is an excellent example of Helsinn’s focus on early-stage investments in areas of high unmet patient need," said Roberto De Ponti, Pharm.D., Head of Corporate New Ventures and Strategic Investments at Helsinn International Services. "We are proud to be able to support OncoResponse in its mission to address an unmet medical need in patients who are partial or non-responders and expand the promise of immunotherapy.

Medivir focuses exclusively on oncology and reorganizes to significantly reduce the cost structure

On October 10, 2016 Medivir AB (Nasdaq Stockholm: MVIR) reported a reorganization of the company and a significant cost reduction in both early research and administrative functions. The board has decided that the company onwards will have an exclusive focus on oncology, utilizing both of Medivir´s technology platforms and competences in protease inhibition and nucleotide-/nucleoside science (Press release, Medivir, OCT 10, 2016, View Source [SID:SID1234515722]). Partnering discussions for all remaining infectious disease assets in the R&D pipeline will be initiated by year-end, as well as for MIV-711 once the phase IIa program has been completed.

The reorganization will result in a total cost reduction of approximately 110 MSEK per year compared to current levels in the affected functions. The exclusive focus on oncology, along with a reduced number of projects in the early stage research portfolio, will lead to a reduction of around 25 positions and cost savings of approximately 60 MSEK vs current spending in the early stages of development. The reduced early research organization creates flexibility to strengthen capabilities in clinical development and will enable broadening the pipeline with oncology projects in clinical phases. At the same time, efficiency improvements in administrative and commercial support functions will generate the additional cost savings of approximately 50 MSEK per year compared to the current levels, impacting around 20 positions.

As a consequence of these changes, a total of around 30 colleagues will unfortunately have to leave the company and affected vacancies will not be filled. A redundancy cost of approximately 20 MSEK related to these organizational changes will be charged in the fourth quarter.

"I believe this reduced cost in early research, and a streamlined therapeutic area focus with a smaller and more cost effective organization, will strengthen Medivir´s position as an efficient oncology company with a growing development pipeline and research platforms for sustainable growth." says Niklas Prager, CEO & President of Medivir. He continues: "Medivir´s ambition is to have a well balanced and broad pipeline from early to late stages of development. We will continue to build on our technology platforms and proven track record of translating projects into value creating partnerships."

Crescendo Biologics and Takeda Enter Collaboration for Humabody®-based Therapeutics Worth up to $790m

On October 10, 2016 Crescendo Biologics Limited (Crescendo), the drug discovery and developer of Humabody-based therapeutics, and Takeda Pharmaceutical Company Limited (TSE: 4502) reported a global, strategic, multi-target collaboration and license agreement for the discovery, development and commercialization of Humabody -based therapeutics for cancer indications with a high unmet medical need (Press release, Takeda, OCT 10, 2016, View Source [SID:SID1234515716]).

Crescendo will use its proprietary transgenic platform and engineering expertise to discover and optimally configure Humabody candidates (Humabody Drug Conjugates and Immuno-Oncology modulators) against multiple targets selected by Takeda.

"We see significant potential in Crescendo and its innovative technology to develop unique, small and customizable Humabody-based therapeutics," said Andrew Plump M.D., Ph.D., Chief Medical and Scientific Officer, Takeda. "Collaborations are critical to helping us achieve our aspiration of curing cancer. Working together with Crescendo will enable us to leverage its important technology to support Takeda’s goal of developing next generation, highly modular and targeted therapies to treat cancer.

"This collaboration with Takeda represents a significant step forward for Crescendo. It provides validation of our transgenic platform and our capabilities to rapidly assemble and configure small, differentiated Humabody-based therapeutics, opening routes to novel biology," said Dr. Peter Pack, CEO, Crescendo Biologics. "As a leading global pharmaceutical company, Takeda brings extraordinary expertise in the oncology area with significant capabilities in developing and delivering novel medicines to patients. This first major collaboration enables us to potentially broaden and accelerate innovative Humabody-based product candidates. "

Under the terms of the agreement, Crescendo is eligible to receive up to $36 million, in a combination of an upfront payment, investment, research funding and preclinical milestones. Takeda will have the right to develop and commercialize Humabody-based therapeutics resulting from the collaboration. Crescendo is also eligible to receive further clinical development, regulatory and sales-based milestone payments of up to $754 million. In addition, Crescendo will be eligible to receive royalties on Humabody-based product sales by Takeda.

Takeda signed agreements with Crescendo Biologics through its wholly-owned subsidiary, Millennium Pharmaceuticals, Inc.

OncoMed Presents Interim Phase 1b Data for Ipafricept and Vantictumab in Pancreatic Cancer at the ESMO 2016 Congress

On October 10, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported the presentation of interim clinical data from its ongoing Phase 1b trials of ipafricept (FZD8-Fc, OMP-54F28) and vantictumab (anti-Fzd, OMP-18R5) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress (Press release, OncoMed, OCT 10, 2016, View Source [SID:SID1234515712]).

Ipafricept and vantictumab are first-in-class Wnt pathways inhibitors that are each being tested in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with previously untreated metastatic pancreatic cancer. Each Phase 1b clinical trial is designed as a dose-escalation study to primarily assess safety and tolerability. Secondary objectives include a preliminary assessment of efficacy and exploratory objectives include the identification of pharmacodynamic and predictive biomarkers.

"In the pancreatic cancer setting, ipafricept and vantictumab in combination with standard-of-care chemotherapy have demonstrated acceptable safety and encouraging early signs of efficacy and biomarker effects," said Jakob Dupont, M.D., Chief Medical Officer. "The data presented at ESMO (Free ESMO Whitepaper), alongside the data presented at ASCO (Free ASCO Whitepaper) for ipafricept and vantictumab, provide evidence supporting the Phase 2 readiness of each drug. Upon the completion of additional dose cohorts and subsequent follow-up, we look forward to presenting an opt-in package to our partner Bayer for these distinct Wnt pathway inhibitors in the first half of next year."

Ipafricept and vantictumab are both part of OncoMed’s collaboration with Bayer Pharma AG. Bayer can elect to exercise its options on ipafricept and vantictumab through completion of Phase 1b trials.

Ipafricept — Interim Phase 1b Data in Pancreatic Cancer
The ipafricept Phase 1b clinical trial has enrolled a total of 22 patients in four dose cohorts. Median follow up for the subjects was 5.9 months (range 0.97-17.5months) as of the data cut-off of August 1, 2016.

Safety
Interim safety results showed that the combination of ipafricept with chemotherapy was well tolerated. The most common toxicities were fatigue, nausea and decreased appetite and vomiting. No Grade 4 or 5 ipafricept-related toxicities were observed. Ipafricept did not appear to enhance chemotherapy-related toxicities.

Following the incidence of bone fractures in the Phase 1a clinical trials of Wnt inhibitors, OncoMed implemented an enhanced bone safety plan that includes monitoring of blood bone markers and bone density, and the administration of zoledronic acid bone protection in at-risk patients. Twelve of 22 patients received bone protective therapy on study and no fragility fractures were observed.

A maximum-tolerated dose has not yet been established and a fourth cohort is currently enrolling.

Efficacy
An interim efficacy assessment demonstrated evidence of anti-tumor effects for the combination of ipafricept with chemotherapy. Of the 18 patients evaluable for response, the overall response rate was 39 percent with seven patients achieving partial response. Another eight patients have achieved stable disease for a clinical benefit rate of 83 percent. Early evidence of durability was observed, with nine patients on study greater than 168 days and two patients on study for greater than one year. Progression-free survival (PFS) and overall survival (OS) data are not yet mature. At the time of the data cut-off eight subjects were still on study treatment.

Biomarker analysis
Interim analysis showed that patients with higher expression of Wnt pathway genes at baseline had greater than 40 percent reduction in tumor size compared to those patients with lower Wnt pathway gene expression at baseline, suggesting activated Wnt pathway signaling at baseline may be predictive of patients with a more favorable response to treatment.

A poster discussion of data from the ipafricept Phase 1b clinical trial was presented on Sunday, October 9, during the Developmental Therapeutics session in a poster titled, "Phase 1b study of WNT inhibitor ipafricept (IPA, decoy receptor for WNT ligands) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC)" (Abstract #3410).

Vantictumab – Interim Phase 1b Data in Pancreatic Cancer:
The vantictumab Phase 1b clinical trial has enrolled a total of 24 patients in four dose cohorts. As of the data cut-off of August 1, 2016 for results reported at ESMO (Free ESMO Whitepaper), median follow up for subjects was 5.9 months (range: 0.77-28.5 months).

Safety
Interim safety results showed that the combination of vantictumab with chemotherapy was well tolerated. The most common vantictumab-related toxicities were fatigue, nausea and dysgeusia. No Grade 4 or 5 vantictumab-related toxicities were observed. Further, vantictumab did not appear to enhance chemotherapy-related toxicities.

Following the incidence of bone fractures in the Phase 1a clinical studies of Wnt inhibitors, OncoMed implemented an enhanced bone safety plan that includes monitoring of blood bone markers and bone density, and the administration of zoledronic acid bone protection in at-risk patients. Seventeen of 24 patients received bone protective therapy and no fragility fractures have been observed.

A maximum-tolerated dose has not yet been established and a fifth cohort is currently enrolling.

Efficacy
An interim efficacy assessment demonstrated evidence of anti-tumor effects for the combination of vantictumab with chemotherapy. Of the 21 patients evaluable for response, the overall response rate was 48 percent with 10 patients achieving partial response. Further, the clinical benefit rate was 86 percent as an additional eight patients achieved stable disease. PFS and OS data are not yet mature. Nine of 24 patients were on study greater than 168 days with two patients on study for more than a year. At the time of the data cut-off five subjects were still on study treatment.

Biomarker analysis
Exploratory interim analysis of baseline tumors suggested OncoMed’s three-gene predictive biomarker successfully identified patients with better overall responses. Of the eight patients whose tumors were positive for the biomarker, seven achieved partial responses and one achieved stable disease.

Data from the vantictumab Phase 1b clinical trial were presented on Saturday, October 8, during the Gastrointestinal Tumors session in a poster titled, "Phase 1b study of WNT inhibitor vantictumab (VAN, human monoclonal antibody) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC)" (Abstract #3412).