BG-00011

Jeremy Moeller/Getty Images Bristol Myers Squibb entered two separate research collaboration and licensing deals, one with San Francisco-based SyntheX and the second with London’s Autolus Therapeutics. Nitpicker/Shutterstock Bristol Myers Squibb entered two separate research collaboration and licensing deals, one with San Francisco-based SyntheX and the second with London’s Autolus Therapeutics . This first partnership will leverage SyntheX’s ToRNeDO platform for protein degradation. The platform discovers molecular glue-based protein degraders using pre-specified E3 ligases and neosubstrates. Molecular glue degraders are compounds that organize interactions between a target protein and an E3 ubiquitin ligase, which causes the degradation of the target protein. Ubiquitin attaches to obsolete proteins, signaling to cells that it’s time for them to be disposed of by breaking them down into their component molecules. BMS is paying upfront cash and an investment in the company. SyntheX is eligible for up to $550 million in performance-based milestones. It is also eligible for royalties based on worldwide net sales of any subsequent commercial products. Maria Soloveychik, Ph.D., SyntheX’s co-founder and CEO said the company looks forward to combining its ToRNeDO platform with BMS’s clinical development expertise as “we work to discover and deliver the next-generation of TPD therapies for patients in need.” The company’s pipeline focuses on oncology and includes STX100 targeting RAD51; STX200 targeting RAF1; STX300 targeting KRASG122X, STX400 targeting NRas; STX500 targeting Cbl-b and STX600 targeting Shoc2. All are in preclinical development. SyntheX’s investors include BMS, SOSV, OMX/Ventures, MorganNoble, Oriza Ventures and 8VC. The Autolus Therapeutics agreement provides BMS with access to Autolus’ RQR8 safety switch, which BMS can then incorporate into specific cell therapies for cancer indications. Toxic side effects, such as cytokine release syndrome and brain toxicity, are common in cell therapies. In these types of cell therapies, such as CAR-T, T-cells are genetically engineered to respond to specific cancer antigens and their epitopes. They are then infused back into the patient, where they become a living therapy, producing more T-cells to attack the cancer cells. But they can grow too fast or too much, which causes severe side effects. Safety switches, such as Autolus’ RQR8, are a way of limiting these side effects by placing limits on T-cell production. “Safety switches are critical to the future of our field of advanced cell therapies,” said Martin Pule, Autolus’ CSO in a prepared statement. “They allow us to develop approaches that are designed to significantly improve patient outcomes, whilst at the same time incorporating the potential to reduce the risk of severe adverse side effects from the treatment .” Autolus’ proprietary RQR8 switched is administered with Genetech and Biogen’s Rituxan (rituximab). Rituxan is approved to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis and pemphigus vulgaris. Once dosed, rituximab binds to the engineered CD20 epitopes on the surface of the cell therapy and triggers selective cell death. RQR8 is a 136-amino-acid epitope-based marker/suicide gene . A suicide gene is genetically coded so that it selectively destroys transferred T cells when facing unacceptable levels of toxicity, a common severe side effect of CAR-T and cell therapies. Specifically, RQR8 is for T-cells and combines target epitopes from both CD34 and CD20 antigens, which allows selection from a clinically approved CliniMACS CD34 system (Miltenyi), a medical device system designed to enrich CD34+ targets. Binding with rituximab, it selectively deletes transgene-expressing cells.

Days after the Cambridge-based company halted its BACE inhibitor program for Alzheimer’s disease, the company stopped another clinical trial in idiopathic pulmonary fibrosis due to safety reasons. The hits keep coming for Biogen . Days after the Cambridge-based company halted its BACE inhibitor program for Alzheimer’s disease, the company stopped another clinical trial in idiopathic pulmonary fibrosis due to safety reasons. First reported by Andrew Dunn of Biopharmadive on Twitter, Biogen noted on clinicaltrials.gov that the mid-stage trial assessing the experimental drug BG00011 against placebo had to be halted for safety concerns . Biogen said on the government website that end-of-study and safety follow-up visits are currently in progress. Biogen acquired the human monoclonal antibody BG00011 in 2012 when the company snapped up Stromedix in a $562.5 million deal. BG00011 was designed to selectively disrupt the TGF-beta pathway, which plays a central role in fibrotic disease. The drug took some time to enter Phase II, but the objective of the trial that has now been halted was to evaluate the efficacy of BG00011, along with several secondary objectives. The secondary objectives included assessing the efficacy of the drug compared to placebo in IPF patients as determined by change in percent predicted forced (expiratory) vital capacity (FVC); to assess progression-free survival in participants who receive BG00011 compared with placebo; to assess the occurrence of IPF exacerbation in participants who receive BG00011 compared with placebo; to assess the incidence of absolute decline in FVC greater than 10% in participants who receive BG00011 compared with placebo, among others. Idiopathic pulmonary fibrosis (IPF) is a fatal disease caused by progressive scarring of the lungs, which makes breathing difficult and prevents the heart, muscles and vital organs from receiving enough oxygen to work properly. The disease can advance quickly or slowly, but eventually, the lungs will harden and stop working altogether. There is no known cure for IPF. The median survival time from diagnosis is two to five years, and the five-year survival rate is approximately 20 to 40%. As noted on Seeking Alpha, RBC’s Brian Abrahams said expectations for the Biogen IPF drug were low, which means there is not an expectation axing the trial will negatively impact the company’s stock. However, Abrahams did say that the fate of BG00011 points out the “relatively high-risk nature of Biogen’s pipeline and removes a potential diversification opportunity.” Biogen had hoped to use the drug to enter a space with few approved products, such as Boehringer Ingelheim’s Ofev (nintedanib), which was first approved for IPF in 2014. Only days ago, the U.S. Food and Drug Administration approved Ofev for systemic sclerosis-associated interstitial lung disease. It is the first and only drug approved for this indication. The other drug approved by the FDA for IPF is Genentech’s Esbriet. That drug, first developed by Brisbane, Calif.-based InterMune, was approved in 2014, two months after Roche acquired the company in an $8.3 billion deal . Esbriet, which was approved under Breakthrough Therapy Designation, inhibits with the production of Transforming Growth Factor-beta, a small protein in the body involved in how cells grow and Tumor Necrosis Factor (TNF)-alpha, a small protein that is involved in inflammation. While Biogen scrapped its IPF drug trial, other companies are in-line to challenge Boehringer Ingelheim and Genentech. In May, AstraZeneca’s IPF-focused saracatinib received Orphan Drug Designation from the FDA. Saracatinib, which is Phase II-ready, is an inhibitor of src kinase which regulates broad cell functions including cell growth and cell differentiation, according to the company.