ADAM17

MUNICH, Germany I November 15, 2023 I SciRhom GmbH , a pioneering biotech enterprise specialized in developing first-in-class therapeutic antibodies, announced today the achievement of a significant milestone in its development pipeline. The company has submitted a Clinical Trial Application for its lead candidate, SR-878, a groundbreaking antibody designed to target iRhom2 as a therapeutic strategy for numerous autoimmune disorders. Dr. Jan Poth, Managing Director & CEO of SciRhom, expressed his gratitude and pride in the development team's outstanding efforts, stating, "We can be proud of what was achieved, and a big thank you goes to our entire team. This milestone allows us to evaluate our promising approach in humans, bringing us one step closer to our ultimate goal of helping patients suffering from autoimmune diseases." iRhom2 is a critical regulator of the enzyme TACE, a master switch for various disease-causing signaling pathways. SR-878, the company's internal code for their lead iRhom2 antibody, simultaneously blocks several of these pathways, among them TNF-α and IL-6R signaling, which are currently targeted individually by drugs approved for autoimmune disorders. Moreover, SR-878 facilitates tissue regeneration and immune re-balancing. Preclinical studies demonstrated the superior efficacy and likely favorable safety profile of SR-878. Results from both in vitro and in vivo models of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) revealed that SR-878 potently and selectively inhibits TACE in immune cells, offering protection against these debilitating conditions. Lupus nephritis and dermatological diseases are further leading indications in SciRhom’s development pipeline. SciRhom has worked to unravel the complexities surrounding iRhom2 that make it a challenging target for antibody development. The submission of the Clinical Trial Application marks the successful completion of that endeavor and all necessary preclinical work packages. Collaborating with WuXi Biologics, the company established a robust biopharmaceutical manufacturing process that consistently produces high yields of SR-878 with excellent antibody properties and remarkable quality. The toxicological characterization of SR-878 confirmed its expected favorable safety profile, with no adverse findings in the 4-week GLP toxicity study. The company's collaboration with external partners was instrumental in reaching this pivotal stage. Dr. Jens Ruhe, Managing Director & COO of SciRhom, emphasized the highly satisfactory teamwork: "The collaborative achievement of our team and expert advisors with WuXi Biologics and other vendors not only underscores the power of teamwork but also exemplifies the remarkable synergy and seamless cooperation of a harmonious and reliable partnership. All parties have been truly exemplary, and we couldn't be more satisfied with the results of our combined efforts." Submission of the Clinical Trial Application paves the way to initiate the first clinical study of SR-878 in humans and is a testament to the company’s unwavering commitment to creating game-changing treatments. About iRhom2 TACE (TNF-alpha converting enzyme or ADAM17) controls several major signaling pathways, including TNF-alpha, IL-6, and EGFR signaling. TACE has, therefore, been considered a potential target to block pro-inflammatory pathways, but direct inhibition of TACE causes severe side effects, such as skin and intestinal lesions. The recent discovery that iRhom2 (inactive Rhomboid 2, RHBDF2) simultaneously regulates the TACE-dependent release of TNF-alpha and of other pro-inflammatory molecules from immune cells provides an exciting opportunity to target the pro-inflammatory activities of TACE while preserving its protective functions. Furthermore, numerous new research studies suggest that iRhom2 is an attractive emerging target for a broad range of therapeutic areas, including immunology, inflammation, oncology, and infectious and metabolic diseases. About SciRhom GmbH SciRhom GmbH, based in IZB Martinsried, Germany, is a biotech company that translates science into the preclinical and early clinical development of novel biopharmaceuticals for the treatment of life-threatening autoimmune diseases. Based on longstanding academic research conducted at the Hospital for Special Surgery (HSS) and a well-established network of experts, SciRhom was founded in 2016 through a collaboration between academic and industry scientists with profound experience in antibody development. Since then, the company has developed first-in-class anti-iRhom2 antibodies and nominated a candidate for clinical studies. Four comprehensive patent families cover the anti-iRhom2 antibodies and iRhom2-target epitopes, securing exclusivity and protection against me-too drugs. To date, SciRhom has successfully acquired seed funding from the High-Tech Gruenderfonds (HTGF), Hospital for Special Surgery, and other institutional and private investors. SOURCE: SciRhom

Improved ADCC with ADAM17 gene knockout of NK or CAR NK cells, supporting ADAM17 KO use for clinical applications Increased specific killing of cancer cells in vitro by the combination of NKX101 and cetuximab,supporting use for combination in solid tumors SOUTH SAN FRANCISCO, Calif., April 17, 2023 (GLOBE NEWSWIRE) -- Nkarta Inc, (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, today announced the presentation of two preclinical data abstracts focused on its natural killer cell pipeline and proprietary manufacturing technology at the 2023 American Association of Cancer Research (AACR) Annual Meeting. "Our AACR presentations demonstrate the potential to combine our engineered, donor-derived NK cell therapies with monoclonal antibodies to extend and enhance the potency of both modalities,” said James Trager, PhD, Chief Scientific Officer of Nkarta. “We have shown that our products maintain high levels of CD16 and that the binding of appropriate monoclonal antibodies to CD16 can expand the targeting and potency of CAR NK cells. Specifically, we’ve shown that NKX101, our clinical candidate engineered with an NKG2D-based CAR, can be combined with cetuximab to enhance activity towards EGFR-expressing tumor cells. We’ve also shown that CRISPR-mediated knockout of ADAM17, a suppressor of CD16 activity, can be used to further elevate ADCC, and to help maintain NK cell potency. These findings will be critical groundwork for developing successful therapeutic combinations that include treatment with CAR NK cells, particularly in solid tumor settings.” Nkarta’s 2023 AACR posters will be available for download shortly after their scheduled presentation at . ADAM17 knockout NK or CAR NK cells augment antibody dependent cellular cytotoxicity (ADCC) and anti-tumor activity Abstract Number 890 April 16, 2023, 1:30 p.m. – 5:00 p.m. ET In this study, ADAM17 KO CAR NK cells demonstrate improved ADCC and ADAM17 KO can enhance in vivo anti-tumor activity of CISH/CBLB KO CD70 CAR NK cells in relevant tumor models. ADAM17 KO NK cells maintain dramatically higher surface expression of CD16a and CD62L than control NK cells. ADAM17 KO CD19 CAR NK cells demonstrate higher cytotoxicity compared to control NK cells against Raji tumor cells in the presence of rituximab (anti-CD20). Similarly, ADAM17 KO CD70 CAR NK cells also possess enhanced cytotoxicity against 786-O tumor cells in the presence of the anti-EGFR antibody, cetuximab. Furthermore, ADAM17/CISH/CBLB triple KO CD70 CAR NK cells have improved antitumor efficacy in vivo in an HL60 AML xenograft model. These data support the further exploration of ADAM17 KO CAR NK cells for clinical application and to improve the efficacy of therapeutic antibodies in combination with the adoptive transfer of engineered NK cells. Combination of anti-EGFR antibody cetuximab with NKX101, an allogeneic NKG2D-L targeting NK cell therapy, enhances potency and in vitro cytotoxicity against solid tumors Abstract Number 3183 April 17, 2023, 1:30 p.m. – 5:00 p.m. ET This study demonstrates that cetuximab, a human IgG1 antibody targeting epidermal growth factor receptor (EGFR) approved for the treatment of colorectal and head and neck cancers, increases the anti-tumor effect of NKX101 in a dose-dependent manner. Assessment of the interaction between NKX101 and cetuximab in vitro revealed that the two agents can combine to kill cancer cells in a synergistic manner. Blocking CD16 on NKX101 cells with a neutralizing antibody significantly decreases the potency of the combination, suggesting that the improvement in potency observed is a direct result of CD16-mediated ADCC activity. It was also demonstrated that common CD16 polymorphisms do not influence NKX101 ADCC activity. This study shows that the combination of an engineered allogeneic NK cell therapy, NKX101, with cetuximab leads to an increase in the specific killing of cancer cells in vitro and supports further investigation into this combination for the treatment of solid tumors. About Nkarta Nkarta is a clinical-stage biotechnology company advancing the development of allogeneic, off-the-shelf natural killer (NK) cell therapies for patients with cancer. By combining its cell expansion and cryopreservation platform with proprietary cell engineering technologies and CRISPR-based genome engineering capabilities, Nkarta is building a pipeline of future cell therapies engineered for deep anti-tumor activity and intended for broad access in the outpatient treatment setting. For more information, please visit the company’s website at . Cautionary Note on Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," “plans,” “potential,” "projects,” “would” and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include, but are not limited to, statements concerning Nkarta’s expectations regarding any or all of the following: the potential benefits of combining NK cell therapies with monoclonal antibodies such as anti-CD16 or anti-EGFR antibodies; the possibility of treating solid tumors with such combination therapies; and the potential benefits of an ADAM17 gene knockout in NK cell therapies. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Nkarta’s limited operating history and historical losses; Nkarta’s lack of any products approved for sale and its ability to achieve profitability; the risk that the results of preclinical studies and early-stage clinical trials may not be predictive of future results; Nkarta’s ability to raise additional funding to complete the development and any commercialization of its product candidates; Nkarta’s dependence on the success of its two lead product candidates, NKX101 and NKX019; that Nkarta may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Nkarta’s ability to obtain, maintain and protect its intellectual property; Nkarta’s dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; the complexity of the manufacturing process for CAR NK cell therapies; and risks relating to the impact on our business of the COVID-19 pandemic or similar public health crises. These and other risks are described more fully in Nkarta’s filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of Nkarta’s Annual Report on Form 10-K for the quarter and year ended December 31, 2022, filed with the SEC on March 16, 2023, and Nkarta’s other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Nkarta undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Nkarta Media/Investor Contact: Greg Mann Nkarta, Inc. gmann@nkartatx.com

Biologic drugs offer quite the punch, treating a wide swath of immunological disorders for patients while bringing in blockbuster sales for drug companies. But these large molecules come as injections or infusions. Dice Therapeutics believes it can address the patient preference for pills by developing small molecule drugs that can hit large molecule targets. The concept has won over investors, enabling the preclinical-stage biotech to raise $204 million in an upsized IPO. Dice Therapeutics, which changed its name from Dice Molecules ahead of the IPO, initially planned to offer 10 million shares in the range of $15 to $17 apiece. The company boosted the number of shares in the deal to 12 million and offered them at the top of the projected price range. Dice’s shares began trading on the Nasdaq Wednesday under the stock symbol “DICE.” In its IPO filing, Dice notes that biologic drugs developed in the late 1990s and early 2000s transformed the treatment of many immunological disorders. But the company added that improvements to the efficacy of these drugs and how frequently they must be dosed still poses a hurdle to patients who don’t want chronic injections or infusions. Developing oral versions of these drugs has been its own challenge, as large molecules such as antibodies can’t be absorbed in the gut. Dice’s proprietary technology, called Delscape, discovers, designs, and develops small molecules that it says have the potential to modulate protein-protein interactions as effectively as large molecules do. The company is developing drugs that go after disease targets that have already been validated for biologic drugs, but the company aims to hit those targets with its small molecules. Lead Dice drug candidate S011806 is designed to block interleukin-17, a pro-inflammatory signaling molecule. Biologic drugs that address this target include two antibodies: Novartis’s Cosentyx and Taltz from Eli Lilly. Those drugs, each approved for multiple immunological disorders, generated about $4 billion and $1.8 billion respectively in revenue last year. In preclinical research, Dice said its small molecule was able to selectively block forms of IL-17 and also match the anti-inflammatory activity of a monoclonal antibody. Now the company aims to see how well its animal research translates to humans. In July, Dice filed a clinical trial application seeking permission to begin human testing of S011806 in the United Kingdom. The company said in the IPO filing that it plans to start a Phase 1 study in healthy volunteers, followed by a Phase 1c clinical trial in patients with psoriasis. Programs in inflammatory bowel disease and idiopathic pulmonary fibrosis are in earlier stages of development with drug candidates yet to be nominated. Other drug targets include interleukin-23, tumor necrosis factor alpha, neonatal Fc receptor, and thymic stromal lymphopoietin. Dice is keeping immunology as the main focus of the company’s internal programs. Expansion into other therapeutic is happening via research partnerships. In 2015, Dice began an immuno-oncology research partnership with Sanofi that gives the phama giant an exclusive option to license, develop, and commercialize compounds that Dice discovers. If Sanofi opts to develop compounds discovered under the alliance, the French company could be responsible for paying its partner up to $200 million tied to development and regulatory milestones, plus royalties from sales of a commercialized product. Dice said in the IPO filing that this research has identified multiple potential drug candidates, and an investigational new drug application is expected by the end of 2023. A partnership Dice inked with Genentech in 2017 has not gone as well. The alliance covered targets selected by the Roche subsidiary. Details about those targets were not disclosed but apparently Genentech did not see anything that from Dice that it liked. As of the end of 2020, Genentech had not requested additional research services nor had it selected any of the customer options available under the contract, Dice said in the filing. Prior to the IPO, Dice had raised about $200 million, according to the prospectus. The largest shareholder after the IPO is RA Capital Management, owning 11.1% of the company followed by Northpond Ventures’ 8.9% stake. As of June 30, Dice reported a cash position of $42.5 million. Combined with the IPO proceeds, the company plans to spend about $90 million for its lead program, S011806, and another $20 million on its programs for inflammatory bowel disease and idiopathic pulmonary fibrosis. The rest of the IPO cash will go toward other research and development work. After IPO, Tyra Bio aims to make cancer drug R&D a “SNAP” Tyra Biosciences, a cancer drug developer, raised $172.8 million from its IPO to bring its most advanced programs into clinical trials. After initially planning to offer 9 million shares in the range of $14 to $16 each, the company found investor interest was strong enough to support increasing the number of shares to 10.8 million, which were offered at the top end of the projected price range. Shares of Carlsbad, California-based Tyra trade on the Nasdaq under the stock symbol “TYRA.” Despite the availability of new targeted cancer treatments, the response rate and the duration of currently available therapies can be limited by drug resistance and other shortcomings, Tyra said in its IPO filing. Tyra’s technology, called SNAP, yields small molecules specifically designed to address acquired drug resistance. According to the prospectus, SNAP efficiently identifies and selectively targets vulnerabilities in mutant proteins where genetic alterations have eliminated or reduced the effectiveness of targeted therapies. These “SNAPshots” give insight into the structure of binding sites for its molecules, telling Tyra scientists how commonly occurring genetic alterations lead to acquired drug resistance to existing drugs. With those insights into the genetic alterations most likely to cause drug resistance, the company designs drug candidates that avoid those mutations but still block the intended target. “Through this process, we identify product candidates that may have the potency and selectivity to, if approved, be used as important treatment options to address critical unmet needs,” Tyra said in the prospectus. The first focus of Tyra is developing small molecules that block fibroblast growth factor receptors (FGFR), a family of proteins that when mutated, drive cancer growth. Lead Tyra program TYRA-300 is designed to block FGFR3; the initial focus for that compound is bladder cancer. The company plans to submit an investigational new drug application in the middle of 2022. Other drugs in the pipeline include compounds targeting FGFR2, FGFR3, RET, and FGFR4. Before the IPO, Tyra had raised $157.2 million, the company said in the IPO filing, most recently a $106 million Series B financing announced in March. The largest shareholders are RA Capital Management and Boxer Capital, each holding a 15.3% post-IPO stake. As of June 30, the company reported having $135.2 million in cash. In the IPO filing, Tyra said it plans to spend $18.9 million for development of TYRA-300 through the completion of the Phase 1 portion of the planned Phase 1/2 clinical trial. Another $19.4 million is set aside for developing the FGFR2 program, also through completion of Phase 1; about $20.8 million will go to advance the FDFR3 program for achondroplasia into the clinic. The rest of the IPO cash will be used for discovery and preclinical development of other drug candidates. Procept and its surgical robot score $164M in stock market debut Procept BioRobotics, a company that was awarded FDA marketing clearance for its surgical robot earlier this year, raised $163.9 million to support its ongoing commercialization efforts. The Redwood City, California-based company was able to boost the size of its IPO. After initially planning to offer 5.5 million shares in the range of $22 to $24 each, Procept ended up offering more than 6.5 million shares at $25 apiece. Those shares trade on the Nasdaq under the stock symbol “PRCT.” The Procept robot, called the AquaBeam Robotic System, was developed to enable minimally invasive urologic surgery, removing prostate tissue in patients who have benign prostatic hyperplasia, or BPH. Development of the technology began in 2009, according to the IPO filing. The robotic system’s features include real-time imaging; ultrasound imaging integrated with planning software that helps the surgeon come up with a tissue removal plan specific to the patient’s anatomy; robotic execution of the procedure under the watch of the surgeon; and ablation of the unwanted tissue using a heat-free water jet that pulses at nearly the speed of sound. AquaBeam was first commercialized overseas; the FDA granted marketing clearance to the Class II medical device in March, according to the IPO filing. Through the end of June, Procept said it had 124 of its systems installed globally and 73 in the U.S. So far, AquaBeam has been used to treat more than 5,500 patients. Procept reported $7.7 million in sales in 2020, a more than 26% increase over the prior year. Sales continue to grow. Revenue in the first half of this year was nearly double the company’s total sales in 2020. With the IPO proceeds, Procept said it plans to spend $45 million to hire more sales and marketing staff; another $25 million is set aside for product development and R&D.