CD19 positive Acute Lymphoblastic Leukemia

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here . Endpoints will be covering #ESMO24 throughout the weekend, so make sure to follow along online. Deputy editor Reynald Castañeda and reporters Kyle LaHucik, Lei Lei Wu and Ayisha Sharma will be reporting from Barcelona. — Max Gelman On Monday, the US House of Representatives passed the Biosecure Act with broad bipartisan support. The bill would force biopharma companies to cut ties or restrict their work with contract manufacturers WuXi AppTec , WuXi Biologics and three genetic sequencing companies by 2032. However, it still faces an uncertain future in the Senate. Opponents have argued that the bill was written to quickly and too broadly. Zachary Brennan has the latest. Biotech’s Covid-19 superstar has faced a rough go of it since the pandemic ended, saying since late last year that it would adopt a more “restrained” approach. But after leading off 2024 with $4 billion in expected cuts, Moderna said this week that it’s planning even more . Executives mapped out an additional $1.1 billion in cuts by 2027 and pushed back the company’s breakeven point by two years, from 2026 to 2028. Moderna’s stock is down more than 80% over the last three years. Our Andrew Dunn also framed how to think about this news in our Post-Hoc newsletter. Our reporters shared updates from #ESMO24, including lackluster data on Amgen’s PRMT5 inhibitor, a Phase 2 look at Jazz’s HER2 antibody, Bicycle’s early case for its Padcev competitor, mid-stage data for GSK and iTeos’ PD-1 and TIGIT doublet , and more. Stay tuned for more conference coverage throughout the weekend. In May, Summit surprised the industry by claiming its PD-1/VEGF bispecific antibody called ivonescimab beat Merck’s Keytruda in a head-to-head Phase 3 study. This Sunday, Summit backed up its case. Ivonescimab reduced the risk of lung cancer progression or death by 49% in the study, with patients going an average of 11.1 months before their disease worsened. Keytruda recorded an average of 5.8 months. Summit’s stock is up more than 800% since the May reveal, and more than 900% for the whole year. Friday afternoon, Jared Whitlock reported that the SEC’s probe of the Illumina-Grail deal is focused on sales forecasts made by Grail’s management in the run-up to the 2021 transaction. In June, Illumina spun off Grail and it began trading as a public company. We covered a string of early-stage GLP-1 readouts this week, including from Roche’s dual GLP-1/GIP candidate which showed promising weight loss, but also high rates of vomiting in a Phase 1b study . Terns also offered an early look at its oral GLP-1 agonist, which it says could be more tolerable at higher doses than currently marketed GLP-1s that are administered the same way. And Zealand’s GLP-1/GLP-2 receptor dual agonist showed promising weight loss after a previous effort with lower doses ended with “underwhelming” efficacy. SPOTLIGHT R&D PHARMA FINANCING FDA DEALS MANUFACTURING HEALTH TECH DON’T MISS

A new startup attempting to develop AAV gene therapies to treat cancer emerged from stealth Thursday morning with $26 million in seed funding — and a plan to quickly get into the clinic. Vironexis Biotherapeutics is aiming to get a Phase 1/2 trial up and running in October for what it describes as an “off-the-shelf” gene therapy, a term that has historically been connected to allogeneic CAR-T. Such therapies have proven difficult to develop, as they continue to face questions about their durability. And the FDA has not approved any. But rather than giving patients re-engineered white blood cells from donors, Vironexis’ gene therapy is designed to deliver an engineered gene. The gene prompts the body to continuously create a protein that links tumor-fighting T cells on one side and tumor cells on the other. CEO Samit Varma likened the process to an immunotherapy that the body produces itself. What Vironexis means by “off-the-shelf” is that there is no individualized manufacturing process for its therapy like for autologous CAR-T, where a patient’s own white blood cells are removed, genetically modified and then readministered, Varma told Endpoints News . Instead, its process allows the therapy to be made in bulk and stored in freezers at treatment sites. “The human immune system is the most powerful drug in the world, and so we’re leveraging that power by introducing this gene that can then identify these tumor cells,” Varma said. Timothy Cripe, a co-founder whose research at Nationwide Children’s Hospital helped launch the company, also said he believes the approach is safer than traditional CAR-T. With the program, called VNX-101, the immune-fighting reaction ramps up more slowly as the protein continues to be expressed and accumulates over time. The first kind of cancer Vironexis wants to attack is CD19-positive acute lymphoblastic leukemia, a setting where two autologous CAR-Ts are currently approved: Novartis’ Kymriah and Gilead and Kite’s Tecartus. Varma said the FDA granted the program IND clearance and that the company already has manufactured enough of VNX-101 to begin the trial next month. Vironexis also plans to expand to other areas at a steady march, and it expects another program called VNX-202 to start a basket trial for HER2-positive cancers in 2025. Design-wise, VNX-202 contains the same AAV delivery vehicle as VNX-101, but researchers replaced the gene responsible for the anti-CD19 proteins with a gene for HER2. Varma said its approach can allow the company to go into many different cancer settings with few modifications. So far, Vironexis has conducted preclinical testing for BCMA-, PSMA- and GD2-positive cancers, among several others. They’re also “actively” in discussions for a Series A, he said, and hopes to raise one “within the next several months.” Also co-founding Vironexis is Brian Kaspar, the former AveXis founder and CSO who helped develop the SMA gene therapy Zolgensma and was let go after it was acquired by Novartis following a data manipulation scandal in 2019. Kaspar has denied any wrongdoing. In an interview Wednesday, Kaspar said he hopes Vironexis can follow the commercialization path AveXis and Novartis laid out with Zolgensma, which he added other gene therapy companies have struggled with. Varma also noted that he’s worked with Kaspar at multiple companies since AveXis and that the due diligence always comes back clean. “This is actually our fourth company, post-AveXis departure, that Brian and I have done together, and in each one of those, it’s been a massive amount of diligence,” Varma said. “It’s been investigated by probably 12 different top law firms in the country, every time we did an acquisition or anytime we raised money.” Drive Capital and Future Ventures led the seed round, with Moonshots Capital and Capital Factory also participating.

CAMBRIDGE, Mass., May 13, 2021 (GLOBE NEWSWIRE) -- TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage cell therapy company with a pipeline of novel T cell therapies for patients suffering from cancer, today announced financial results for the first quarter ended March 31, 2021 and provided a corporate update. “We remain on track to identify the recommended Phase 2 dose for gavo-cel in 2021 and advance into the expansion portion of the Phase 1/2 trial where our primary focus will be efficacy as well as continuing to monitor for safety. The clinical benefit we have observed with our cancer patients gave us confidence to expand our manufacturing capabilities by establishing a commercial-scale cGMP facility in Rockville, Maryland, which we expect to come online in 2023,” said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. “In the last quarter we were also able to showcase our early-stage programs in our rich pipeline and reflect on the versatility of our TRuC-T cell platform. This included presenting our CD70-targeted autologous TRuC-T cell and our mesothelin-targeted allogeneic TRuC-T cell at AACR. As for our additional solid tumor milestones in 2021, we expect to present more complete data from the dose escalation Phase 1 portion of the gavo-cel trial, file an IND for TC-510, a mesothelin-targeted TRuC-T cell enhanced with a PD-1:CD28 switch receptor, and present preclinical data on our IL-15 enhancement, which we believe will drive even longer persistence and expression of a memory phenotype, characteristics which could be beneficial across our portfolio.” Recent Developments gavo-cel: Early-Stage Pipeline Corporate: Anticipated Milestones Financial Highlights Rockville Facility In March 2021, we entered into a lease for a new manufacturing facility. The landlord built an approximately 85,000 square foot rental building in Rockville, Maryland and leased the facility to the Company as a manufacturing facility for an initial term of 15 years through June 2036. Because we are involved in the construction project and are responsible for paying a significant portion of the costs of normal finish work and structural elements of the facility, the Company is deemed for accounting purposes to be the owner of the building during the construction period under build to suit lease accounting guidance under ASC 840, Leases. Therefore, the Company recorded a construction-in-progress asset and a related construction financing obligation on our consolidated balance sheets as a component of property and equipment and lease financing obligations, respectively. We anticipate lease payments of $1.4 million for the remainder of 2021. About TCR2 Therapeutics TCR2 Therapeutics Inc. is a clinical-stage cell therapy company developing a pipeline of novel T cell therapies for patients suffering from solid tumors or hematological malignancies. TCR2’s proprietary T cell receptor (TCR) Fusion Construct T cells (TRuC®-T cells) specifically recognize and kill cancer cells by harnessing signaling from the entire TCR, independent of human leukocyte antigens (HLA). In preclinical studies, TRuC-T cells have demonstrated superior anti-tumor activity compared to chimeric antigen receptor T cells (CAR-T cells), while secreting lower levels of cytokine release. The Company’s lead TRuC-T cell product candidate targeting solid tumors, gavo-cel, is currently being studied in a Phase 1/2 clinical trial to treat patients with mesothelin-positive non-small cell lung cancer (NSCLC), ovarian cancer, malignant pleural/peritoneal mesothelioma, and cholangiocarcinoma. The Company’s lead TRuC-T cell product candidate targeting hematological malignancies, TC-110, is currently being studied in a Phase 1/2 clinical trial to treat patients with CD19-positive adult acute lymphoblastic leukemia (aALL) and with aggressive or indolent non-Hodgkin lymphoma (NHL). For more information about TCR2, please visit . Forward-looking Statements This press release contains forward-looking statements and information within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as "may," "will," "could", "should," "expects," "intends," "plans," "anticipates," "believes," "estimates," "predicts," "projects," "seeks," "endeavor," "potential," "continue" or the negative of such words or other similar expressions can be used to identify forward-looking statements. These forward-looking statements include, but are not limited to, express or implied statements regarding the therapeutic potential of gavo-cel, timing for interim updates for the gavo-cel and TC-110 clinical trials, timing for the certification of our manufacturing facility in Stevenage, UK and Rockville, MD, increased manufacturing capacity and technical capabilities, including relating to our manufacturing partnership with ElevateBio, LLC, increased clinical trial demand, future IND filings and clinical development plans, the development of the Company’s TRuC-T cells, their potential characteristics, applications and clinical utility, and the potential therapeutic applications of the Company’s TRuC-T cell platform. The expressed or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical studies and in the availability and timing of data from ongoing clinical studies; whether interim results from a clinical trial will be predictive of the final results of the trial; whether results from preclinical studies or earlier clinical studies will be predictive of the results of future trials; the expected timing of submissions for regulatory approval or review by governmental authorities, including review under accelerated approval processes; orphan drug designation eligibility; regulatory approvals to conduct trials or to market products; TCR2’s ability to maintain sufficient manufacturing capabilities to support its research, development and commercialization efforts, including TCR2’s ability to secure additional manufacturing facilities; whether TCR2's cash resources will be sufficient to fund TCR2's foreseeable and unforeseeable operating expenses and capital expenditure requirements, the impact of the COVID-19 pandemic on TCR2’s ongoing operations; and other risks set forth under the caption "Risk Factors" in TCR2’s most recent Annual Report on Form 10-K, most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although TCR2 believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither TCR2 nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. Investor and Media Contact: Carl MauchDirector, Investor Relations and Corporate Communications(617) 949-5667carl.mauch@tcr2.com TCR2 THERAPEUTICS INC.UNAUDITED CONSOLIDATED BALANCE SHEETS(amounts in thousands, except share data) TCR2 THERAPEUTICS INC.UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS(amounts in thousands, except share and per share data) TCR2 THERAPEUTICS INC.UNAUDITED CONSOLIDATED STATEMENTS OF CASH FLOWS(amounts in thousands)