CBL B inhibitor (HotSpot Therapeutics)

BOSTON, March 14, 2023 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," today announced it will present two poster presentations on the company's CBL-B program at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, FL. One poster will describe preclinical data for the CBL-B program, and one Clinical Trials in Progress poster will describe the first-in-human Phase 1/2 clinical trial of HST-1011. Presentation details are as follows: Title: Inhibition of the E3 ligase CBL-B enhances the effector function and proliferation of natural killer cells Session Title: Late-Breaking Research: Immunology 3 Session Date and Time: Wed., Apr. 19, 9:00 AM-12:30 PM ET Location: Poster Section 36 Poster Board Number: 5 Abstract Number: LB337 Title: Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD1 in patients with advanced solid tumors Session Title: Phase I and First-in-Human Clinical Trials in Progress Session Date and Time: Tue., Apr. 18, 1:30-5:00 PM ET Location: Poster Section 46 Poster Board Number: 14 Abstract Number: CT251 About HST-1011 HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011's ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot's proprietary Smart AllosteryTM platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL. About HotSpot Therapeutics, Inc. HotSpot Therapeutics, Inc. is pioneering a new class of allosteric drugs that target certain naturally occurring pockets on proteins called "natural hotspots." These pockets are decisive in controlling a protein's cellular function and have significant potential for new drug discovery by enabling the systematic design of potent and selective small molecules with novel pharmacology. The Company's proprietary Smart Allostery™ platform combines computational approaches and AI-driven data mining of large and diverse data sets to uncover hotspots with tailored pharmacology toolkits and bespoke chemistry to drive the rapid discovery of novel hotspot-targeted small molecules. Leveraging this approach, HotSpot is building a broad pipeline of novel allosteric therapies for the treatment of cancer and autoimmune diseases. To learn more, visit . Investor & Media Contact: Natalie Wildenradt [email protected] SOURCE HotSpot Therapeutics

Demonstrated NX-2127 overcomes BTK inhibitor resistance mutations and provides clinical benefit to patients with hematological malignancies Achieved significant milestones in wholly owned clinical programs and partnered preclinical programs Maintained strong financial position with year-end cash and marketable securities totaling $373 million SAN FRANCISCO, Feb. 09, 2023 (GLOBE NEWSWIRE) -- Nurix Therapeutics Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, today reported financial results for the fourth quarter and fiscal year ended November 30, 2022 and provided a corporate update. “In 2022, Nurix achieved multiple ‘firsts’ in oncology with our drug candidates, establishing Nurix as the leader in the targeted protein modulation field,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “Clinical data from Nurix’s NX-2127 Bruton’s tyrosine kinase degrader program demonstrated the ability to overcome BTK inhibitor resistance mutations including those lacking catalytic function, resulting in the first evidence from a BTK degrader of clinical benefit in CLL patients with no alternative approved therapies. We have also established mechanistic proof of concept with our first-in-class CBL-B inhibitor. In 2023, we look forward to maintaining the momentum we have built as we continue to advance our pipeline for patients with significant unmet medical needs in both hematologic malignancies and solid tumors.” Recent Business Highlights Provided updated clinical data from NX-2127 Bruton’s tyrosine kinase (BTK) degrader program at the American Society of Hematology (ASH) Annual Meeting: In December 2022, two oral presentations were given at the ASH meeting by Nurix collaborators Anthony Mato, M.D., MSCE, former director of the Chronic Lymphocytic Leukemia (CLL) Program at Memorial Sloan Kettering Cancer Center, and Omar Abdel-Wahab, M.D., Chair of Sloan Kettering Institute (SKI) Molecular Pharmacology Program at Memorial Sloan Kettering Cancer Center. Specifically, the first presentation described positive data from the ongoing Phase 1 trial of NX-2127 demonstrating clinically meaningful objective responses in a heavily pretreated patient population harboring multiple BTK inhibitor resistance mutations. The second presentation detailed the variety of emerging BTK inhibitor resistance mutations identified in the trial, all of which remain susceptible to BTK degradation. These new scientific findings support the rationale for BTK degradation as a novel mechanism of action to address the current and emerging unmet need in patients whose cancer has relapsed following multiple prior lines of therapy. Presented clinical data from NX-5948 BTK degrader program andexpanded geographical reach of ongoing clinical trial: At an analyst event held by Nurix at the ASH Annual Meeting, Nurix presented initial PK/PD data from the Phase 1 clinical trial of NX-5948 in adults with relapsed or refractory B-cell malignancies demonstrating early evidence of target engagement with rapid and sustained BTK degradation in all patients and no evidence of immunomodulatory-associated adverse events. An archived webcast of the event, which also covered the ASH Annual Meeting presentations of NX-2127 data, can be accessed via the Events and Presentations page of the Investor section of the Nurix website. In addition, in December 2022, Nurix announced that it received clearance from the U.S. Food and Drug Association (FDA) for its investigational new drug (IND) application to expand the drug candidate’s Phase 1a/1b trial, which is ongoing in the United Kingdom, into sites in the United States. The trial is designed to evaluate the safety and tolerability of NX-5948 in adults with relapsed and refractory B-cell malignancies. Presented multiple posters highlighting data from Nurix’s Casitas B-lineage lymphoma proto-oncogene (CBL-B) inhibitor programs at the Society for Immunotherapy of Cancer (SITC) Annual Meeting: At the SITC Annual Meeting in November 2022, Nurix presented six posters focused on its CBL-B inhibitor programs, including initial biomarker data demonstrating successful target engagement of CBL-B in patients treated in the ongoing Phase 1 clinical trial of NX-1607. The development and implementation of a novel proprietary biomarker indicate that the doses of NX-1607 currently being tested in the study are achieving biologic activity anticipated to be within the therapeutic range based on the results from relevant animal models. Completed safety run-in portion of the Phase 1 clinical trial of DeTIL-0255: In November 2022, Nurix announced the successful completion of the safety run-in portion of the Phase 1 clinical trial of DeTIL-0255 in patients with advanced gynecologic malignancies. Based on the preliminary safety pro DeTIL-0255 and feedback from the FDA, Nurix may explore a potential combination of NX-1607 with cell therapy. Advanced preclinical discovery programs with collaboration partners Gilead Sciences and Sanofi: Nurix is advancing ten discovery programs under its collaboration partnerships with Gilead Sciences and Sanofi. Of its ten partnered programs, Nurix has options to co-develop and co-promote a total of four programs in the United States. Throughout 2022, Nurix made significant progress within its collaborations as evidenced by the receipt of multiple milestone payments from both partners. Upcoming Program Highlights* NX-2127: Nurix’s lead drug candidate from its protein degradation portfolio, NX-2127, is an orally bioavailable degrader of BTK with immunomodulatory activity for the treatment of patients with relapsed or refractory B-cell malignancies. Nurix anticipates presenting additional clinical results in the second half of 2023. Nurix also anticipates defining a regulatory strategy for NX-2127 in the second half of 2023 based on emerging clinical data and feedback from the FDA. Additional information on the clinical trial can be accessed at (NCT04830137). NX-5948: Nurix’s second drug candidate from its protein degradation portfolio, NX-5948, is an orally bioavailable BTK degrader designed without immunomodulatory activity for certain B-cell malignancies and autoimmune diseases. Nurix is evaluating NX-5948 in a Phase 1 clinical trial in adults with relapsed or refractory B-cell malignancies and expects to present initial clinical data from the Phase 1a portion of the study in the second half of 2023. In addition, Nurix expects to define a dose for Phase 1b cohort expansion. Additional information on the clinical trial can be accessed at (NCT05131022). NX-1607: Nurix’s lead drug candidate from its targeted protein elevation portfolio, NX-1607, is an orally bioavailable inhibitor of the E3 ligase CBL-B for immuno-oncology indications including a range of solid tumor types and lymphoma. Nurix is evaluating NX-1607 in an ongoing, Phase 1 trial in adults with a variety of oncology indications and expects to present clinical data from the Phase 1a portion of the study and to define a dose for Phase 1b cohort expansion in the second half of 2023. Additional information on the clinical trial can be accessed at (NCT05107674). Selection of new drug candidate: Nurix expects to select a new targeted protein degrader development candidate in 2023. Continued advancement of strategic collaborations with Gilead Sciences and Sanofi: Nurix expects to continue to achieve substantial research collaboration milestones throughout 2023 from its collaborations with Gilead Sciences and Sanofi. * Expected timing of events throughout the press release are based on calendar year quarters. Fiscal Fourth Quarter and Full Year 2022 Financial Results Collaboration revenue for the three months and twelve months ended November 30, 2022 was $6.8 million and $38.6 million, respectively, compared with $7.4 million and $29.8 million for the three and twelve months ended November 30, 2021, respectively. The increase for the twelve-month period was primarily due to the continued scale up of internal resources and external spending for Nurix’s collaborations with Gilead Sciences and Sanofi as compared to the prior year, resulting in a higher percentage of completion in the current year. During the year ended November 30, 2022, Nurix achieved several research milestones under its collaboration with Gilead and Sanofi totaling $10 million and $3 million, respectively. Research and development expenses for the three months and twelve months ended November 30, 2022 were $46.1 million and $184.5 million, respectively, compared with $36.5 million and $116.4 million for the three and twelve months ended November 30, 2021, respectively. The increase for the twelve-month period was primarily related to an increase in compensation and personnel costs, including in non-cash stock-based compensation expense, attributable to an increase in headcount, an increase in clinical and contract manufacturing costs due to ramping up of our clinical programs and patient enrollment, an increase in supplies and contract research cost and preclinical activities, and an increase in facility and other costs primarily due to the expansion of leased premises and investments in information technology. General and administrative expenses for the three months and twelve months ended November 30, 2022 were $9.4 million and $38.0 million, respectively, compared with $8.8 million and $31.2 million for the three and twelve months ended November 30, 2021, respectively. The increase for the twelve-month period was primarily related to compensation expenses including an increase in non-cash stock-based compensation, which were primarily attributable to higher headcount and the issuance of restricted stock units and incentive stock options. Net loss for the three months and twelve months ended November 30, 2022 was $46.7 million or ($0.87) per share and $180.4 million or ($3.71) per share, respectively, compared with $37.7 million or ($0.85) per share and $117.2 million or ($2.73) per share for the three and twelve months ended November 30, 2021, respectively. Cash, cash equivalents and marketable securities was $373.0 million as of November 30, 2022, compared with $432.9 million as of November 30, 2021. About Nurix Therapeutics, Inc. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of small molecule and cell therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit /. Forward Looking Statements This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding Nurix’s future financial or business performance; Nurix’s future plans, prospects and strategies; Nurix’s current and prospective drug candidates; the planned timing and conduct of our clinical trial programs for our drug candidates; the planned timing for the provision of clinical updates and findings from our clinical studies; the potential advantages of Nurix’s DELigase™ platform and drug candidates; and the extent to which Nurix’s scientific approach and DELigase™ platform may potentially address a broad range of diseases. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions regarding the future of Nurix’s business, future plans and strategies, its development plans, its preclinical and clinical results, future conditions and other factors Nurix believes are appropriate in the circumstances. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) risks and uncertainties related to Nurix’s ability to advance its drug candidates, obtain regulatory approval of and ultimately commercialize its drug candidates; (ii) the timing and results of preclinical studies and clinical trials; (iii) Nurix’s ability to fund development activities and achieve development goals; (iv) the impact of macroeconomic conditions, including inflation, increasing interest rates and volatile market conditions, and global events, including the ongoing COVID-19 pandemic, on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (v) Nurix’s ability to protect intellectual property and (vi) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Annual Report on Form 10-K for the year ended November 30, 2022, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law. Contacts: Investors Silinda Neou Nurix Therapeutics ir@nurixtx.com Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors lwolffe@wheelhouselsa.com Media Aljanae Reynolds Wheelhouse Life Science Advisors areynolds@wheelhouselsa.com Nurix Therapeutics, Inc. Condensed consolidated statements of operations (in thousands, except share and per share amounts) (unaudited) Three Months Ended November 30, Year Ended November 30, 2022 2021 2022 2021 Collaboration revenue $ 6,783 $ 7,396 $ 38,627 $ 29,750 Operating expenses: Research and development 46,106 36,531 184,497 116,434 General and administrative 9,367 8,818 37,997 31,202 Total operating expenses 55,473 45,349 222,494 147,636 Loss from operations (48,690 ) (37,953 ) (183,867 ) (117,886 ) Interest and other income, net 1,973 295 3,507 823 Loss before income taxes (46,717 ) (37,658 ) (180,360 ) (117,063 ) Provision for income taxes — 44 — 131 Net loss $ (46,717 ) $ (37,702 ) $ (180,360 ) $ (117,194 ) Net loss per share, basic and diluted $ (0.87 ) $ (0.85 ) $ (3.71 ) $ (2.73 ) Weighted-average number of shares outstanding, basic and diluted 53,944,109 44,554,325 48,607,990 42,895,383 Nurix Therapeutics, Inc. Condensed consolidated balance sheets (in thousands) (unaudited) November 30, 2022 2021 Assets Current assets: Cash and cash equivalents $ 64,474 $ 80,506 Marketable securities, current 244,667 215,214 Accounts receivable — 6,000 Income tax receivable — 204 Prepaid expenses and other current assets 9,308 9,194 Total current assets 318,449 311,118 Marketable securities, non-current 63,879 137,189 Operating lease right-of-use assets 12,345 14,005 Property and equipment, net 17,163 11,340 Restricted cash 901 286 Other assets 4,022 2,833 Total assets $ 416,759 $ 476,771 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 5,064 $ 6,650 Accrued expenses and other current liabilities 22,428 14,549 Operating lease liabilities, current 5,530 3,847 Deferred revenue, current 37,633 41,212 Total current liabilities 70,655 66,258 Operating lease liabilities, net of current portion 6,434 9,189 Deferred revenue, net of current portion 35,974 59,022 Total liabilities 113,063 134,469 Stockholders’ equity: Common stock 47 45 Additional paid-in-capital 709,220 563,757 Accumulated other comprehensive loss (4,319 ) (608 ) Accumulated deficit (401,252 ) (220,892 ) Total stockholders’ equity 303,696 342,302 Total liabilities and stockholders’ equity $ 416,759 $ 476,771