On January 4, 2019 MabVax Therapeutics Holdings, Inc. (OTC Pink: MBVX), a clinical-stage immuno-oncology drug development company with a fully human antibody discovery platform focused on the clinical development of products to address unmet medical needs in the treatment of cancer and pancreatitis, reported that it has entered into discussions to merge with Oncotelic, Inc., a privately held cancer immunotherapy company (Press release, MabVax, JAN 4, 2019, View Source [SID1234532459]). Oncotelic is developing a unique TGF-b antisense therapy which has demonstrated the ability to break immune tolerance in mid-stage clinical trials for the treatment of glioblastoma and pancreatic cancer.

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Based on terms of a non-binding letter of intent signed by both companies on January 3, 2019, MabVax and Oncotelic are entering discussions to combine the companies to form a publicly traded company focused on the development of proprietary immunotherapy-based products of both companies to diagnose and treat cancer. Under the terms of the letter of intent, Oncotelic will merge with a wholly-owned subsidiary of MabVax in an all-stock transaction and will become a wholly-owned subsidiary of MabVax. The merger is subject to the approval of the MabVax board of directors and achieving certain financing objectives and other customary conditions. Upon closing of the transaction, MabVax will be re-named Oncotelic, Inc. and will operate under the leadership of the combined Oncotelic and MabVax management teams, with Vuong Trieu, founder of Oncotelic, an experienced and successful biotechnology entrepreneur, as executive chairman. Certain current senior management team members at MabVax will remain with the merged companies to fill key operational roles.

On a pro forma basis, calculated at the close of the merger, the current MabVax stockholders will own 25% and Oncotelic stockholders will own 75% of the combined company, respectively. The merger agreement contemplates securing financing of at least $10 million simultaneous with execution of the merger to support the clinical development of Trabedersen, Oncotelic’s TGF-b antisense therapy, in both glioblastoma and pancreatic cancer trials.

Vuong Trieu, Ph.D., who will be executive chairman of the company post-merger, said, "Our goal has been to grow a strong RNA therapeutic company that leverages innate immunity to achieve durable and effective immunotherapies for solid tumors and the merger with MabVax will allow us to complement that effort with key programs and capabilities from MabVax that will significantly strengthen the effort."

David Hansen, President and CEO of MabVax, said, "Through this transaction we hope to leverage our clinical and operational expertise in the post-merger company to advance the clinical development of Trabedersen while also integrating the development of key assets discovered by MabVax. This will allow us to continue the process of realizing the maximum value of assets we have developed through a process already initiated with Objective Capital while simultaneously maximizing the value of our lead technologies for stockholders."

On December 13, 2018, MabVax announced that it had engaged Objective Capital Partners, LLC to serve as a financial advisor to assist MabVax in exploring the sale of clinical and preclinical assets of the Company with the goal of maximizing the value of these assets within the near term. MabVax’s lead monoclonal antibody product, 5B1 for the treatment of pancreatic cancer, could be one of the assets that potentially could be developed into later stage clinical trials by the combined company.

On January 4, 2019 KalGene Pharmaceuticals Inc., a biotechnology company developing therapeutics to slow the progression of Alzheimer’s disease, reported the appointment of James Callaway, Ph.D. as chief executive officer, effective immediately (Press release, KalGene Pharma, JAN 4, 2019, View Source [SID1234532493]).

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"This has been a very important transition year as we have confirmed our initial thesis with respect to validating the company’s lead KG207, which in pre-clinical studies was shown to successfully cross the blood brain barrier and safely reduce plaque load. The company has successfully completed early toxicology studies and has carried out all the requisite steps to manufacture product," said Dr. Jacki Jenuth, Chairperson of the Kalgene’s board of directors. "We are very pleased to have executed on the next key step of our strategy in attracting an accomplished new CEO to the company as we leverage this foundation and address significant inbound interest for the company and its lead program. Jim brings an ideal set of leadership skills and domain expertise to guide the team through the transition from a pre-clinical to a clinical stage company."

"KG207 has shown exceptional potential in pre-clinical studies, and I am excited about the prospect of bringing such a promising compound into the clinic," Dr. Callaway commented. "I look forward to working with the savvy and talented team at KalGene as we strive to make a difference in the lives of individuals affected by Alzheimer’s disease."

Dr. Callaway has over three decades of biopharmaceutical development experience, primarily targeting CNS therapeutics, and has served most recently as CEO for two privately-held biotech companies. As the CEO of ArmaGen, he brought its products from the laboratory to the clinic, helping the company emerge as the first to demonstrate the ability of engineered biologics to cross the blood-brain barrier. In addition, Dr. Callaway led the Alzheimer’s immunotherapy program at Elan Pharmaceuticals, which became the first company to introduce disease-modifying biologics (e.g., AN1792, bapinuzumab, ACC001) into clinical studies. Dr. Callaway has filed and defended numerous NDAs and INDs during his career, including shepherding the approval of MyoBloc and the production of Tysabri. He previously served in senior development roles at Bayer Pharmaceuticals, SmithKline Beecham (GSK), and InGene (since acquired by Xoma Corporation). He holds a Ph.D. in Biological Chemistry from UCLA, with a focus on peptide chemistry

On January 4, 2019 BerGenBio ASA (OSE: BGBIO), reported that the first patient has been dosed in an investigator-initiated phase II trial of bemcentinib, a selective, potent and orally bio-available AXL inhibitor, in patients with high-risk myelodysplastic syndrome (MDS) who have failed first-line treatment with hypomethylating agents (Press release, BerGenBio, JAN 4, 2019, View Source [SID1234532440]). The trial may also enrol a proportion of patients with acute myeloid leukaemia (AML). The study is being sponsored by GWT-TUD GmbH (a specialist cancer clinical research institution associated with the University of Dresden, Germany) with the support of BerGenBio.

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The trial (BGBIL009 / BERGAMO) aims to confirm the efficacy of bemcentinib monotherapy in patients with high-risk MDS and AML and will enrol up to 43 patients at 8 hospitals in Germany, France, the Netherlands and Italy. The study will allow for the evaluation of potential predictive and pharmacodynamic biomarkers for MDS in bone marrow and blood, including those associated with patient benefit from bemcentinib.

Prof. Uwe Platzbecker, lead investigator of the trial and director of the Medical Clinic and Policlinic 1, Hematology and Cell Therapy at the University Hospital in Leipzig, Germany, commented: "As treatment of MDS and AML has not changed significantly over the past decades, novel therapies are urgently needed. The survival is still dismal, especially in elderly patients who are not eligible for allogeneic stem cell transplantation and who have failed first line treatment with hypomethylating agents. AXL, a member of the Tyro3, AXL, Mer (TAM) receptor family, mediates proliferation and survival of leukemic cells and is upregulated upon cytostatic treatment. Pre-clinical studies with the inhibitor bemcentinib demonstrated in vitro and in mouse models that leukaemic proliferation was blocked by interference with AXL signalling. Hence, AXL represents a promising new target for the patient population investigated in the BERGAMO trial."

Richard Godfrey, Chief Executive Officer of BerGenBio, added: "We are very pleased that Prof. Platzbecker and GWT-TUD are initiating this study, which if positive will add valuable information on bemcentinib’s monotherapy use in a larger leukaemia population and provide support for our broader development plans for bemcentinib in these indications. We look forward to reporting results as the trial progresses."

END

About MDS
Myelodysplastic syndromes (MDS) are stem cell disorders characterised by a decreased ability of the bone marrow to produce normal blood cells and platelets. MDS is associated with increased risk of developing AML and immune dysfunctions are seen in patients both with lower and higher-risk MDS. Drugs that modify immunological responses can improve blood values and prolong survival in some patients. Thus far, however, the only curative treatment for MDS remains stem cell transplantation. Hence, there is an urgent need for novel therapies to treat MDS.

About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying aggressive and life-threatening diseases. In cancer, AXL drives tumour survival, treatment resistance and spread, as well as suppressing the body’s immune response to tumours. AXL expression has been established as a negative prognostic factor in many cancers. AXL inhibitors, therefore, have potential value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities.

About Investigator-sponsored trials
Investigator-sponsored clinical trials are clinical trials proposed by front-line patient-facing physicians who act as the regulatory sponsor and are supported by industry in bespoke clinical development partnerships. The industry partner does not assume the role of sponsor according to European or US regulatory guidelines but may offer support in a variety of different ways, such as providing investigational medicinal product at no cost

On January 4, 2019 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported "2020 Blueprint," a two-year strategy to launch Blueprint Medicines’ global commercial business (Press release, Blueprint Medicines, JAN 4, 2019, View Source [SID1234532460]). Under this strategy, by the end of 2020, the company expects to have two marketed products and at least four additional marketing applications pending in the United States and Europe. In addition, Blueprint Medicines reported recent milestones and key goals through 2020 across its differentiated portfolio of investigational precision therapies.

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"Our vision is to rapidly evolve Blueprint Medicines into the leading global precision therapy company, with a robust scientific platform reproducibly designing innovative compounds and an effective and nimble commercial organization delivering a portfolio of important medicines to patients worldwide," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "As we enter the new year, we are at the precipice of this transformation with the planned submission of our first new drug application for our lead therapeutic candidate avapritinib and growing momentum in building our commercial capabilities. Combined with seven ongoing or planned registration-enabling clinical trials for avapritinib and BLU-667, we believe Blueprint Medicines is well-positioned to quickly capitalize on this first potential regulatory approval and realize our goal of becoming a portfolio-based commercial-stage company."

"2020 Blueprint" Global Business Strategy

The "2020 Blueprint" strategy establishes a path to transform Blueprint Medicines into a global commercial enterprise focused on delivering a portfolio of precision therapies to patients with cancer and rare diseases. Under this strategy, Blueprint Medicines anticipates achieving the following by the end of 2020:

2 marketed products in the United States and 1 marketed product in Europe
4 additional marketing applications pending in the United States and Europe
6 therapeutic candidates in global clinical development
8 research programs that leverage strategic areas of focus
"Our ‘2020 Blueprint’ strategy extends to our ongoing research efforts, where we are advancing multiple programs designed to complement our scientific and clinical expertise and planned commercial profile," said Marion Dorsch, Ph.D., Chief Scientific Officer of Blueprint Medicines. "Under this strategy, we have three research areas of focus: franchise opportunities in gastrointestinal stromal tumors, systemic mastocytosis and lung cancer where we believe our understanding of mutational drivers gives us an advantage; cancer immunotherapy under our ongoing collaboration with Roche; and novel genetic drivers that we characterize and target with our differentiated scientific platform."

Recent Portfolio Milestones and Key Goals through 2020

RECENT MILESTONES:

Blueprint Medicines today announced:

Top-line results from the Phase 1 NAVIGATOR clinical trial of avapritinib in patients with advanced gastrointestinal stromal tumors (GIST), as of a data cutoff date of November 16, 2018. These data will be used to support the submission of a planned new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the first half of 2019 for the treatment of patients with PDGFRA Exon 18 mutant GIST, which primarily includes PDGFRα D842V GIST, and fourth-line GIST. The primary endpoints for registration are objective response rate (ORR) and duration of response (DOR) based on central radiology and modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST 1.1) criteria.
In 43 patients with PDGFRA Exon 18 mutant GIST treated with a starting dose of 300 or 400 mg once daily (QD), the ORR was 86 percent (one response pending confirmation). Median DOR was not reached.
In 111 patients with fourth-line GIST treated with a starting dose of 300 or 400 mg QD, the ORR was 22 percent (one response pending confirmation). Median DOR was 10.2 months.
Top-line safety results were consistent with those previously reported. Avapritinib was well-tolerated, and most adverse events (AEs) reported by investigators were Grade 1 or 2. Across all doses (n=237), only 23 patients (9.7 percent) discontinued treatment with avapritinib due to treatment-related AEs.
Two registration-enabling clinical trials for avapritinib in systemic mastocytosis (SM) are now underway. The first clinical site recently opened for the Phase 2 PIONEER clinical trial for patients with indolent and smoldering SM, and initial patient screening for this trial is anticipated in January 2019. In addition, patient dosing has been initiated in the Phase 2 PATHFINDER clinical trial for patients with advanced SM.
As part of the collaboration with CStone Pharmaceuticals, the China National Medicinal Products Administration has approved an investigational new drug (IND) application for the ongoing global Phase 1 trial of BLU-554 in advanced hepatocellular carcinoma. The companies expect to initiate patient enrollment in the trial by the middle of 2019.
The FDA has cleared an IND application for BLU-782, a selective ALK2 inhibitor in development for patients with fibrodysplasia ossificans progressiva (FOP), and the company plans to initiate a Phase 1 clinical trial in healthy volunteers in the first quarter of 2019.
KEY GOALS:

Blueprint Medicines reported the following key goals and anticipated milestones through 2020:

Avapritinib: advanced gastrointestinal stromal tumors

Submit an NDA to the FDA for PDGFRA Exon 18 mutant GIST and fourth-line GIST in the first half of 2019.
Present additional data from the Phase 1 NAVIGATOR trial in the first half of 2019.
Complete enrollment of the Phase 3 VOYAGER trial in third- or fourth-line GIST in the second half of 2019.
Initiate the Phase 3 COMPASS-2L precision medicine trial in second-line GIST in the second half of 2019.
Submit an NDA to the FDA for third-line GIST in 2020.
Avapritinib: systemic mastocytosis

Present updated data from the Phase 1 EXPLORER trial in advanced SM in the first half of 2019.
Present initial data from the Phase 2 PIONEER trial in indolent and smoldering SM in the second half of 2019.
Complete enrollment of the Phase 2 PATHFINDER trial in advanced SM in the second half of 2019.
Submit an NDA to the FDA for advanced SM in 2020.
BLU-667: RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other solid tumors

Present updated data from the Phase 1 ARROW trial in RET-altered cancers in the first half of 2019.
Complete enrollment of previously treated NSCLC and MTC cohorts in the Phase 1 ARROW trial in the first half of 2019.
Initiate a Phase 3 trial in first-line RET-fusion NSCLC in the second half of 2019.
Initiate a Phase 2 combination trial of BLU-667 and osimertinib in treatment-resistant, EGFR-mutant NSCLC harboring an acquired RET alteration in the second half of 2019.
Submit an NDA to the FDA for second-line RET-fusion NSCLC and second-line RET-mutant MTC in the first half of 2020.
BLU-554: advanced hepatocellular carcinoma

Enroll the first patient in China in the ongoing global Phase 1 trial of BLU-554 under the collaboration with CStone Pharmaceuticals by the middle of 2019.
Initiate a Phase 1 combination trial of BLU-554 and CS-1001, CStone Pharmaceuticals’ anti-PD-L1 inhibitor, in China in the second half of 2019.
BLU-782: fibrodysplasia ossificans progressiva

Initiate a Phase 1 trial in healthy volunteers in the first quarter of 2019.
Initiate a Phase 2 trial in patients with FOP in the first half of 2020.
Research portfolio

Provide an update on the company’s robust and diverse research portfolio, including disclosure of up to two new targets, at a Blueprint Medicines Research and Development day in 2019.
Nominate at least one new wholly-owned discovery program in 2019.

On January 4, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s investigational new drug application (IND) for ARV-110, an oral androgen receptor (AR) PROTAC protein degrader, for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Arvinas, JAN 4, 2019, View Source [SID1234532476]). Arvinas expects to begin enrollment of a Phase 1 clinical trial for ARV-110 in the first quarter of this year.

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"This IND clearance is a key step forward for Arvinas and for the field of protein degradation," said John Houston, Ph.D., President and CEO of Arvinas. "Our PROTAC platform has demonstrated exciting promise in preclinical studies and represents an entirely new approach to treating patients with mCRPC and many other diseases. We hope ARV-110 will deliver a much-needed new therapeutic option for patients, and we expect to dose our first patient in the first quarter of 2019."

ARV-110 was developed using Arvinas’ proprietary technology platform – PROTAC (proteolysis-targeting chimera) protein degraders – that uses small molecules to harness the body’s own natural protein recycling system (the ubiquitin proteasome system) to selectively and efficiently remove disease-causing proteins. ARV-110 is a PROTAC protein degrader specifically designed to target and degrade AR, and has demonstrated activity in preclinical models of AR overexpression and AR mutations, which are both common resistance mechanisms to current standard-of-care agents in men with prostate cancer. The Phase 1 study will investigate the safety and tolerability of ARV-110 in patients with mCRPC who have progressed on at least two standard of care treatment regimens and includes exploratory measures of efficacy.