MT-3724

It’s been several months since a treatment-related death led the FDA to put a partial hold on Molecular Templates’ only first-generation engineered toxin body (ETB) candidate. Now the company is nixing the program, and Takeda is returning the rights to one of its next-gen candidates. MT-3724, Molecular’s EBT in development for non-Hodgkin lymphoma, will be no more, the company said on Monday morning. The FDA first placed a partial hold on the candidate in November, following the death of a Phase II patient who experienced Grade 5 capillary leak syndrome. “Markedly high pharmacokinetic assay readings were observed in this and other subjects treated with a specific lot of MT-3724 material,” according to Molecular. The agency followed up with a full hold in late March, and requested additional information and the development of a new quantitative assay specific to MT-3724, which Molecular says “would take significant time and investment away” from its priorities. $MTEM shares dropped more than 25% on the news Monday. In the same announcement, Molecular said Takeda is backing out of a collaboration deal for TAK-169, a second-generation ETB targeting CD38 for the treatment of multiple myeloma. Takeda forked over $30 million upfront for the partnership back in 2018, and promised milestones up to $632.5 million. Takeda is turning the full rights over to Molecular, which will owe Takeda “low-single digit royalties” on future net sales. The drug, which was designed to overcome tumor resistance observed with Janssen and Genmab’s daratumumab (the first approved monoclonal antibody targeting CD38), is in a Phase I study. According to Molecular, Takeda says its decision to back out of the partnership was the result of “ongoing portfolio prioritization.” So far, Takeda has enrolled and treated four subjects in the TAK-169 Phase I study, and Molecular says there have been no life-threatening toxicities or signs of CLS. Molecular’s EBTs use genetically engineered versions of the Shiga-like Toxin A subunit. They go after cancer cells and also add antigens into the cancer cells themselves, helping prime the immune system to target them for destruction. CEO and CSO Eric Poma says the company plans to “take immediate steps to accelerate new site activation and patient enrollment in the TAK-169 study to generate data this year.” — Nicole DeFeudis Charles River partners with Valence to provide AI discovery platform Big-name CDMO Charles River Laboratories has swung another deal, this time giving its clients access to a new AI platform. The Wilmington, MA-based firm has teamed up with Valence Discovery, the companies announced Tuesday, in an effort to expand Valence’s AI platform for molecular property prediction, generative chemistry and multiparameter optimization. Financial terms of the deal were not disclosed. Valence says its platform enables the design of small molecule drugs in new regions of chemical space, allowing for rapid optimization against potency, selectivity, safety and pharmacology criteria on a project-by-project basis. Companies taking advantage of Charles River’s CDMO offerings can opt into the Valence program. Charles River has been busy to start off 2021, securing a $104 million buyout of Distribution Bio in January and Cognate in an $875 million acquisition in February. — Max Gelman With topline PhII data in hand, Scholar Rock races toward pivotal trial launch Scholar Rock says it got the topline Phase II data it was looking for with its spinal muscular atrophy (SMA) drug apitegromab, and is racing to launch a pivotal trial by the end of this year. The Phase II trial enrolled patients across three cohorts: patients between 5 and 21 years old with ambulatory type 3 SMA; patients between 5 and 21 years old with type 2 and non-ambulatory type 3 SMA who started the treatment nusinersen when they were older than 5 years old; and patients older than 2 years old with type 2 SMA who initiated nusinersen younger than 5. In the first cohort, patients received either apitegromab either as a monotherapy or in combo with nusinersen. A total of 57% of patients observed a maintenance or improvement on the Revised Hammersmith Scale (RHS), and 22% of patients achieved at least a 3-point increase in RHS score from baseline, according to Scholar Rock. In Cohort 2, which excluded one patient who was also receiving an acetylcholinesterase inhibitor and one who missed consecutive doses due to Covid-19, the mean change from baseline on Hammersmith Functional Motor Scale Expanded was a 1.2-point improvement. And in Cohort 3, where patients either received a low or high dose of apitegromab in combination with nusinersen, the mean change from baseline in HFMSE score was a 7.1-point and a 5.3-point improvement for the 20 mg/kg and 2 mg/kg dose arms, respectively. The majority (59%) of patients in Cohort 3 achieved at least a 5-point increase in HFMSE and 35% of patients achieved greater than a 10-point increase in HFMSE over baseline, according to Scholar Rock. That analysis also excluded three patients who had missed doses due to Covid-19 challenges. Apitegromab aims to boost muscle mass and strength in SMA patients by inhibiting the growth factor myostatin, which breaks down muscle mass in the body. “These top-line 12-month data provide further support towards establishing apitegromab as a potential first muscle-directed therapy for patients with SMA,” CMO Yung Chyung said in a statement. “The findings also offer important insights into myostatin biology and our scientific approach of targeting the latent forms of growth factors. — Nicole DeFeudis Sorrento Therapeutics snaps up a late-stage TKI in ACEA Therapeutics buyout Sorrento Therapeutics is buying out ACEA Therapeutics — and with it, a late-stage tyrosine kinase inhibitor, an extensive library of small molecules, and a 23-acre cGMP facility in Quzhou, China. The companies began talking about the merger back in October, and officially signed the agreement on Monday. With the deal, $SRNE is snapping up abivertinib, a small molecule TKI that was originally discovered using ACEA’s compound library. The candidate has completed a Phase III trial in NSCLC, and is currently in Phase II for Covid 19-induced respiratory compromise in the US and Brazil. It’s also getting AC0058, a next generation BTK inhibitor currently in a Phase Ib trial for lupus. — Nicole DeFeudis

AUSTIN, Texas, March 18, 2021 (GLOBE NEWSWIRE) -- Molecular Templates, Inc. (Nasdaq: MTEM, “Molecular Templates,” or “MTEM”), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), today reported financial results for the fourth quarter of 2020. “In 2020 and early 2021, we made important progress by advancing our pipeline programs, establishing a new collaboration with a premier oncology partner, and strengthening our balance sheet with a successful equity financing,” said Eric Poma, Ph.D., Molecular Templates’ Chief Executive and Scientific Officer. “We now have four clinical stage programs: MT-5111 targeting HER2, TAK-169 targeting CD38 in co-development with Takeda, MT-6402 with antigen seeding targeting PD-L1, and MT-3724, for which we are working to resolve the FDA partial clinical hold. We expect to generate clinical data from multiple programs and advance our earlier stage programs in 2021, including filing an IND for an ETB targeting CTLA-4, preclinical data presentations on ETBs against new targets, and continued progress in our collaborations with Bristol Myers Squibb, Vertex, and Takeda.” Company Highlights and Upcoming Milestones Corporate MT-5111 (HER2 ETB) TAK-169 (CD38 ETB) MT-6402 (PD-L1 ETB with antigen seeding) MT-3724 (CD20 ETB) Research Financial Results The net loss attributable to common shareholders for the fourth quarter of 2020 was $28.4 million, or $0.57 per basic and diluted share. This compares with a net loss attributable to common shareholders of $15.9 million, or $0.41 per basic and diluted share, for the same period in 2019. Revenues for the fourth quarter of 2020 were $3.5 million, compared to $6.2 million for the same period in 2019. Revenues for the fourth quarter of 2020 were comprised of revenues from collaborative research and development agreements with Takeda and Vertex. Total research and development expenses for the fourth quarter of 2020 were $22.3 million, compared with $16.6 million for the same period in 2019. Total general and administrative expenses for the fourth quarter of 2020 were $7.1 million, compared with $6.0 million for the same period in 2019. As of December 31, 2020, MTEM’s cash and investments totaled $93.9 million. With the addition of the $70 million upfront payment from Bristol Myers Squibb received in 1Q21 and the proceeds of the public equity offering completed in February 2021, MTEM’s current cash and investments are expected to fund operations into the second half of 2023. About Molecular Templates Molecular Templates is a clinical-stage company focused on the discovery and development of targeted biologic therapeutics. Our proprietary drug platform technology, known as engineered toxin bodies, or ETBs, leverages the resident biology of a genetically engineered form of Shiga-like Toxin A subunit to create novel therapies with potent and differentiated mechanisms of action for cancer and other serious diseases. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Molecular Templates disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Act’s Safe Harbor for forward-looking statements.  All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Molecular Templates may identify forward-looking statements. Examples of such statements include, but are not limited to, statements relating to the potential lifting of the partial clinical hold on Molecular Templates’ MT-3724 clinical trials; our investigation into MT-3724 product attributes and potential plans for our MT-3724 studies; statements regarding the safety or potential efficacy of Molecular Templates’ drug or biologic candidates; statements relating to the development of MT-3724, MT-5111, TAK-169, and MT-6402; the expected timing of submitting various IND applications and conducting studies and generating data; the expected participation and presentation at upcoming conferences; the anticipated effects of the COVID-19 pandemic on Molecular Templates’ ongoing clinical studies, manufacturing and preclinical development; and Molecular Templates’ belief that its proprietary biologic drug platform technology, or ETBs, provides for a differentiated mechanism of action that may address some of the limitations associated with currently available cancer therapeutics. Forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors including, but not limited to, Molecular Templates’ ability to satisfactorily respond to requests from the FDA for further information and data regarding MT-3724 on the timeline expected or at all; successfully resolve the partial clinical hold with regard to MT-3724; the uncertainties inherent in the preclinical and clinical development process; whether Molecular Templates’ cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; the ability of Molecular Templates’ to protect its intellectual property rights; risks from global pandemics including COVID-19; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in Molecular Templates’ filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Molecular Templates specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise. Contact:Adam CutlerChief Financial Officeradam.cutler@mtem.com862-204-4006 Molecular Templates, Inc. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except share and per share data) (unaudited) Molecular Templates, Inc. CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands, except share and per share data)