With an increasingly aging global population, neurological disorders have become a major cause of death and disability worldwide. Despite the significant investments that continue to be made in research and development in the neurological field, the discovery of new drugs targeting many CNS disorders, including Alzheimer’s and Parkinson’s diseases, has proved to be difficult. Often the share values of companies in that area can exhibit wild swings related to success or failure in clinical trials. In addition, the COVID-19 pandemic is requiring companies to readjust their clinical trial schedules and programs. Those pressures have weighed on members of the BioWorld Neurological Diseases index, which has slipped about 4% in value so far this year.

Product approvals

About six months after Epizyme Inc. won FDA clearance of Tazverik (tazemetostat) for epithelial sarcoma, the firm scored accelerated approval in the larger indication of relapsed or refractory follicular lymphoma. Specifically, U.S. regulators cleared the methyltransferase inhibitor for adults whose tumors test positive for an EZH2 mutation who have received at least two prior systemic therapies and for those with no satisfactory alternative treatment options.

Evoke Pharma Inc. gained FDA approval for Gimoti (metoclopramide), a nasal spray formulation of metoclopramide designed to inhibit dopamine D2 and serotonin 5-HT3 receptors, for adults with acute and recurrent diabetic gastroparesis.

The FDA approved checkpoint blocker Keytruda (pembrolizumab, Merck & Co. Inc.) “for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.”

Pharmamar SA and partner Jazz Pharmaceuticals plc received an accelerated FDA approval of Zepzelca (lurbinectedin) to treat relapsed metastatic small-cell lung cancer patients. The approval potentially triggers a $250 million payment to Pharmamar based on its commercialization deal signed with Jazz last December. It also offers a new option for patients, having shown a 35% overall response rate (ORR). The historical ORR rate for the chemotherapy topotecan is 16.9%. Zepzelca, an alkylating drug that binds guanine residues within DNA, will be used specifically for those adult patients with disease progression during or following platinum-based chemotherapy.

COVID-19 developments

The EU has secured a supply of the most advanced COVID-19 vaccine in development, in a deal with Astrazeneca plc for up to 400 million doses of AZD-1222, with deliveries starting by the end of 2020. The agreement has been signed with the “inclusive vaccines alliance” formed by Germany, France, Italy and the Netherlands, but will also make AZD-1222 available for other countries in Europe. While the four countries spearheaded this negotiation, on June 12, EU health ministers gave the European Commission a mandate to negotiate advance purchase agreements for up to six different COVID-19 vaccines, for all member states, using a €2.3 billion (US$2.6 billion) emergency fund.

Just 80 days after first issuing an emergency use authorization (EUA) for oral formulations of chloroquine phosphate (CQ) and hydroxychloroquine sulfate (HCQ) in treating COVID-19, the FDA said it is revoking that authorization in light of clinical data and scientific literature that raised questions about whether benefits of the treatment outweigh the risks. Following the review, the agency determined that the suggested dosing regimens for CQ and HCQ detailed in earlier health provider fact sheets are unlikely to produce an antiviral effect.

In the first major breakthrough in therapeutics for COVID-19 infection, dexamethasone has been shown to have a statistically significant impact on mortality in the most seriously ill patients. There was a one-third reduction in deaths in patients on ventilators, while in patients receiving oxygen therapy there was a 15% reduction in 28-day mortality, in the U.K. Recovery trial. No benefit was seen in patients who were sick enough to be in the hospital but did not need help breathing. The steroid was delivered either orally or intravenously at a dose of 6 mg per day. In total, 2,104 patients were randomized to the active arm and 4,321 to standard of care. There were no serious treatment-related adverse events.

Berg LLC plans to tap into the Summit supercomputer located at the Department of Energy's Oak Ridge National Laboratory to conduct drug discovery research in the fight against COVID-19. Cascade Chemistry Inc. has been selected to produce the active pharmaceutical ingredient for clinical trial supplies of RBT-9, Renibus Therapeutics Inc.’s investigational therapy entering a phase II trial for the treatment of COVID-19 patients who are at high risk of deteriorating health due to age or co-morbid conditions such as kidney or cardiovascular disease. Catalent Inc. will provide Astrazeneca plc vial filling and packaging capacity to prepare for large-scale commercial supply of the University of Oxford’s adenovirus, vector-based COVID-19 vaccine candidate AZD-1222. Cobra Biologics Ltd. signed a supply agreement with Astrazeneca to provide GMP manufacture of AZD-1222. The production agreement is part of Astrazeneca's recently disclosed, in-licensed program with the University of Oxford to ensure broad and equitable supply of the vaccine throughout the world, at no profit during the COVID-19 pandemic. Shares of Humanigen Inc. climbed 30.2% last week after the company disclosed that, when treated with the company's anti-GM-CSF antibody, lenzilumab, 12 hospitalized patients with severe or critical pneumonia as a result of COVID-19 showed "rapid clinical improvement." Median time to recovery and discharge for the group was five days. The research, based on compassionate use of the experimental therapy at Mayo Clinic, precedes a registration-directed phase III trial in COVID-19 pneumonia patients that the company is currently enrolling. Sinovac Biotech Ltd. said the preliminary results of the phase I/II trials of its COVID-19 inactivated vaccine candidate, Coronavac, demonstrated favorable immunogenicity and safety profiles. The company said it aims to move it to phase III trials outside China next month. The positive results were unveiled less than two months after the study started. Staidson Biopharma Inc. and European CRO Pivotal said they are collaborating to assess Staidson’s BDB-001, a monoclonal anti-C5a antibody, in a Europe-based clinical trial in progressive severe COVID-19. Treos Bio Ltd. has developed a preventive COVID-19 peptide vaccine, PolyPEPI-SCoV-2, and has transferred all rights, including pending patent applications, to a newly formed subsidiary, Peptc Vaccines Ltd.

Deals of the week

The worldwide option and license agreement Alpine Immune Sciences Inc. drew up with Abbvie Inc. for ALPN-101, a dual CD28/ICOS co-stimulation antagonist for treating systemic lupus erythematosus and other autoimmune diseases, pushed up the company’s stock and supports its planned operations into 2023. Alpine, which had been in discussions with Abbvie for years, will receive an up-front $60 million payment and could receive up to an aggregate of $805 million for exercise of the option and success-based development, regulatory and commercial milestones.

Assembly Biosciences Inc. is regaining worldwide rights to all microbiome gastrointestinal programs licensed under its collaboration agreement with North Chicago-based Abbvie Inc. following the pharma’s decision to terminate the research, development, collaboration and license agreement inked with Allergan plc in 2017. Allergan was acquired by Abbvie. Assembly notes that the move was not based on any efficacy, safety or other data related to the collaboration programs.

Celltrion Inc. aims to wrap up its first major M&A deal with Takeda Pharmaceutical Inc. by the end of the year, pending approvals. The deal will see Takeda take in an initial $266 million in cash, and up to an additional $12 million in milestone payments. Celltrion’s Singapore arm inked the agreement with Takeda to acquire the latter’s Asia-Pacific primary care portfolio consisting of 12 prescription and six over-the-counter pharmaceutical products. The 18 products generated FY2 2018 net sales of around $140 million and include Nesina (alogliptin) and Actos (pioglitazone) for diabetes; Edarbi (azilsartan medoxomil) for hypertension; and Whituben (acetaminophen/dextromethorphan hydrobromide hydrate/guaifenesin/pseudoephedrine hydrochloride/triprolidine hydrochloride hydrate) for colds and Albothyl (policresulen) for stomatitis.

Glaxosmithkline plc will collaborate in three of Ideaya Biosciences Inc.’s synthetic lethality programs, MAT2A (methionine adenosyltransferase 2a), Pol Theta (polymerase theta) and Werner Helicase. Synthetic lethality, one of GSK’s four core research areas in oncology, involves cells tolerating the loss of single genes in isolation but not in combination. Ideaya projects all three programs could reach the clinic within the next three years. It will receive a $100 million up-front cash payment and a $20 million equity purchase of its common stock in a direct private placement. Ideaya also receives a potential $50 million cash option exercise fee for the MAT2A program along with potential preclinical, clinical and sales milestones.

Foundation Medicine Inc. has acquired Lexent Bio Inc., which is developing multiomics liquid biopsy platforms for treating cancer. Lexent's monitoring platform is in development and is based on low-pass whole genome sequencing and DNA methylation analysis.

GNS Healthcare Inc. and the Multiple Myeloma Research Foundation (MMRF) said they entered a five-year partnership to leverage the longitudinal multimodal patient registry data from the MMRF CoMMpass study, the largest genomics dataset of any cancer, with GNS' causal artificial intelligence (AI) and simulation platform to create the next generation of individual patient-level computer models of disease progression and drug response

Immunomic Therapeutics Inc. and Ichor Medical Systems entered a license agreement supporting development of Immunomic’s investigational plasmid DNA vaccine therapy, ITI-1001. Immunomic will use Ichor’s platform to increase cellular uptake of ITI-1001, which targets the pp65, IE-1 and gB viral antigens of cytomegalovirus expressed in glioblastoma.

Neurocrine Biosciences Inc. is paying Takeda Pharmaceutical Co. Ltd. $120 million up front for an exclusive license to seven programs, including three clinical-stage assets targeting the notoriously difficult indications of schizophrenia and treatment-resistant depression, as well as depression-related anhedonia. Neurocrine will develop and commercialize all of the prospects, and Takeda could be in line for $495 million more if development goals are met, plus as much as $1.4 billion in commercial milestone payments and up to double-digit royalties.

Oncolys Biopharma Inc. has sublicensed the nucleoside reverse transcriptase inhibitor OBP-601 to Transposon Therapeutics Inc. for up-front, development and sales milestone payments in excess of $300 million. Sarepta Therapeutics Inc. and Selecta Biosciences Inc. entered a research license and option agreement granting Sarepta an option to license the rights to develop and commercialize Selecta’s immune tolerance platform, ImmTOR, for use in Duchenne muscular dystrophy and certain limb-girdle muscular dystrophies. Sernova Corp. completed an acquisition of cellular local immune protection technology from Converge Biotech Inc., gaining all IP associated with Converge’s conformal coating cell encapsulation technology.

Financial transactions

Public offerings: Avidity Biosciences Inc. closed its IPO that raised gross proceeds of approximately $298.1 million. Celldex Therapeutics Inc. closed its public offering for gross proceeds of about $150 million. Chemocentryx Inc. generated net proceeds of approximately $325.4 million from a follow-on offering. Constellation Pharmaceuticals Inc. priced an underwritten public offering for expected gross proceeds of $192.5 million. For its IPO, Forma Therapeutics Holdings Inc., which is developing therapeutics to treat rare hematologic diseases and cancers, offered 13.8 million shares at $20 each and expects gross proceeds to be about $277.6 million. Generation Bio Co. closed its IPO, raising approximately $230 million. Ideaya Biosciences Inc. priced a public offering for gross proceeds of about $100 million. Iveric Bio Inc. priced an upsized public offering for expected gross proceeds of about $143.9 million. Repare Therapeutics Inc., which identifies synthetic lethal precision oncology targets for drug candidates, completed its IPO, pricing 11 million common shares at the high end of an adjusted $18 to $20 range. Gross proceeds are expected to be about $220 million. Therapeutics Acquisition Inc. filed to raise up to $100 million in an IPO. Royalty Pharma Inc. raised $2.2 billion in an IPO by offering 77.7 million shares at $28 each. The company offered 7.7 million more shares than expected. Vaxcyte Inc. closed its IPO for gross proceeds of $287.5 million.

Other public offerings: Novavax Inc. entered an agreement to sell series A convertible preferred stock, convertible into 4.38 million shares of common stock, to an investment fund affiliated with RA Capital Management in a private placement, for gross proceeds of approximately $200 million.

Venture funding: 4D Molecular Therapeutics Inc., which is working on the development of precision guided AAV gene medicines based on directed evolution, closed a $75 million series C financing led by Viking Global Investors. C4 Therapeutics Inc., a company focused on destroying disease-causing proteins via degradation, has closed a $170 million financing intended to help move four cancer candidates into the clinic by the end of 2022. Etherna Immunotherapies NV raised €34 million (US$38.2 million) in a series B funding round to progress its pipeline of mRNA-based vaccines for cancer and infectious disease. Greenlight Biosciences Inc. raised an oversubscribed $102 million round of funding from new and existing investors to expand production of its RNA products for agricultural and life sciences applications, including an expansion into new RNA-based therapies. Immvira Group Co. completed a $58 million series B financing led by Huagai Capital. Ona Therapeutics SL raised €30 million (US$33.9 million) in a series A round, providing the means to advance a new method of treating metastases by blocking the lipid metabolism of cancer cells. Orca Bio Inc. raised $192 million from a series D round. Shattuck Labs Inc. closed a $118 million series B equity financing led by Redmile Group. Surrozen Inc., a startup developing regenerative medicines leveraging tissue specific Wnt modulation, has raised $50 million in series C financing.

Regulatory news

The U.S. Patent and Trademark Office (USPTO) launched a new program to advance the initial examination of applications for trademarks and service marks used to identify qualifying COVID-19 medical products and services. The program is open to applications for products subject to FDA approval for use in the prevention or treatment of COVID-19 or a medical or medical research service to prevent or treat the coronavirus infections. In addition to expediting the examination, the USPTO will waive the fee for the petitions.

The U.S. District Court for the Northern District of West Virginia ruled against Biogen Inc. and in favor of Mylan NV in a patent dispute regarding Biogen’s blockbuster multiple sclerosis drug, Tecfidera (dimethyl fumarate). The court ruled that Mylan “has established by clear and convincing evidence that the asserted claims of the [8,399,514] Patent are invalid for lack of written description,” thereby invalidating the patent, which provides exclusivity protection to the drug until February 2028. Biogen can appeal the decision, which analysts expect will take 12 to 18 months.

Word on the Street: Industry responses to the issues of the week

“This is an extremely welcome result. The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients. Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.”
Peter Horby, professor of emerging infectious diseases at Oxford University, and one of the chief investigators for the U.K. Recovery trial

"Entrepreneurs just need someone to give them a chance. The sponsors of those Golden Tickets give those companies a chance to prove that what they're going after is possible, and without that opportunity some companies might not exist."
Robert Blazej, director at MBC Biolabs and a partner at Mission Bay Capital, on the Golden Ticket program in which recipients receive 12 months of lab bench space and access to core facilities at MBC Biolabs' incubator, paid for by multiple large drug companies that sponsor the program

“Inventors and entrepreneurs are working around the clock to develop products that will help prevent, diagnose, treat or cure COVID-19. Accelerating initial examination of COVID-19-related trademark applications for these products … will help to bring important and possibly life-saving treatments to market more quickly.”
Andrei Iancu, director, U.S. Patent and Trademark Office

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