Cbl-b

NX-5948 received Fast Track designation from the FDA NX-5948 showed positive results in Phase 1 clinical trial establishing a robust foundation for advancement in CLL Licensed to Gilead a new development candidate, NX-0479/GS-6791, a targeted protein degrader of IRAK-4 for rheumatoid arthritis Formed strategic collaboration with Seagen (now Pfizer) to advance a portfolio of degrader-antibody conjugates based on our industry-leading DELigase platform Achieved $100 million in non-dilutive capital from partners in 2023, including $60 million upfront from Seagen and $40 million in success-based milestones and licensing fees from Gilead and Sanofi Maintained strong financial position with cash and investments of $295.3 million SAN FRANCISCO, Feb. 15, 2024 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today reported financial results for the fiscal quarter and fiscal year ended November 30, 2023, and provided a corporate update. “Building on a very successful 2023, marked by impressive clinical data for both NX-5948 and NX-2127, Nurix has hit the ground running in 2024, with plans to accelerate enrollment in the NX-5948 leukemia and lymphoma program and enable development in inflammatory diseases,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “2023 was also a great year for our partnerships, generating significant non-dilutive funding and expanding our pipeline in both oncology and inflammation with our IRAK-4 degrader. We anticipate continued success with our partners Gilead, Sanofi, and Pfizer in the coming year.” Recent Business Highlights Nurix presented clinical data for Bruton’s tyrosine kinase (BTK) degrader NX-5948 at the American Society of Hematology (ASH) Annual Meeting: In December 2023, Nurix reported data from the dose escalation stage of the Phase 1 trial demonstrating dose-dependent pharmacokinetics (PK), resulting in rapid, robust, and sustained BTK degradation in all patients treated. NX-5948 was well-tolerated across all doses. Preliminary efficacy data demonstrated clinical benefit in six of seven patients with chronic lymphocytic leukemia (CLL). Durable responses were seen across indications in non-Hodgkin lymphoma (NHL) patients, with almost half the patients continuing to receive treatment as of the data cut-off date. Dose escalation in the NX-5948 trial continues across all indications and the study is actively enrolling patients in the United States, the United Kingdom, and the Netherlands.NX-5948 received U.S. FDA Fast Track designation: In January 2024, the FDA granted Fast Track designation for NX-5948 for the treatment of adult patients with relapsed or refractory CLL or small lymphocytic lymphoma after at least two lines of therapy, including a BTK inhibitor (BTKi) and a B-cell lymphoma 2 (BCL2) inhibitor. The FDA’s Fast Track designation is intended to facilitate and expedite the development and review of drug candidates to treat serious conditions and fulfill an unmet medical need. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.Nurix presented clinical data for NX-2127, a dual BTK and IKZF1/3 degrader, at the ASH Annual Meeting: In December 2023, Nurix reported data from its Phase 1a dose escalation and Phase 1b dose expansion cohorts in CLL, mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). NX-2127 exhibited dose-dependent PK, leading to robust and sustained degradation of BTK and biologically relevant degradation of IKZF1 (Ikaros). Treatment with NX-2127 resulted in encouraging rapid and durable responses in the heavily pre-treated patient population including patients with BTK inhibitor resistance mutations. Durable complete responses were reported in two patients with MCL and DLBCL which remained ongoing for over one year. NX-2127 had a manageable safety profile that was consistent with previous reports for BTK-targeted and immunomodulatory therapies.High profile publications provide scientific basis for BTK scaffold function and degrader mechanism: In February 2024, Nurix announced the publication of a manuscript in the journal Science titled: “Kinase Impaired BTK Mutations Are Susceptible to Clinical Stage BTK and IKZF1/3 Degrader NX-2127” that elucidates a previously unappreciated oncogenic scaffold function of BTK responsible for clinical resistance to enzymatic inhibitors and shows that NX-2127 can overcome this resistance across a broad range of acquired mutations. A second manuscript was published contemporaneously in The Journal of Medicinal Chemistry entitled “Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton’s Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies,” which details the discovery and optimization of NX-2127. Upcoming Program Highlights* NX-5948: NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. In 2024, Nurix expects to define doses for Phase 1b cohort expansion in CLL and NHL and accelerate Phase 1 clinical trial enrollment to enable pivotal trials. Nurix plans to present additional clinical data with higher dose levels and longer treatment duration in mid-2024. In addition, Nurix expects to complete ongoing preclinical studies that can enable an investigational new drug (IND) application for NX-5948 in autoimmune indications. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).NX-2127: 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 is conducting a Phase 1a/b clinical trial of NX-2127, which includes three Phase 1b expansion cohorts in patients with DLBCL, MCL and CLL. Screening and enrollment of new study participants have been paused due to a partial clinical hold placed on the study by the FDA. Patients currently enrolled in the clinical study who are deriving clinical benefit may continue to receive treatment in accordance with the ongoing study protocol. In 2024, Nurix expects to resolve the partial clinical hold to enable the introduction of newly manufactured drug product into the ongoing Phase 1 clinical trial. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).NX-1607: Nurix’s lead drug candidate from its targeted protein elevation portfolio, NX-1607, is an orally bioavailable inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (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 monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications. In 2024, Nurix expects to present data from the Phase 1a dose-escalation portion of the trial of NX-1607 and to define dose(s) to enable Phase 1b cohort expansion. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).NX-0479/GS-6791: GS-6791 (previously NX-0479) is a potent, selective, oral IRAK4 degrader. Degradation of IRAK4 by GS-6791 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s partner, Gilead, is responsible for conducting IND-enabling studies and advancing this program to clinical development.Selection of new drug candidate: Nurix expects to select a new targeted protein degrader development candidate in 2024.Continued pipeline advancement of strategic collaborations with Gilead, Sanofi and Pfizer: Nurix expects to continue to achieve substantial research collaboration milestones throughout the terms of its collaborations with Gilead, Sanofi and Pfizer. * Expected timing of events throughout this press release is based on calendar year quarters. Fiscal Fourth Quarter and Full Year 2023 Financial Results Revenue for the three months and twelve months ended November 30, 2023, was $15.2 million and $77.0 million, respectively, compared with $6.8 million and $38.6 million for the three and twelve months ended November 30, 2022, respectively. The increase for the twelve-month period was primarily due to a higher percentage of completion of performance obligations and an increase in the value of milestones achieved in the current period. The increase was also due to the receipt of $20.0 million related to the license option exercise payment from Gilead. During the year ended November 30, 2023, Nurix achieved research milestones under its collaborations with Gilead and Sanofi totaling $12.5 million and $7.0 million, respectively. Research and development expenses for the three months and twelve months ended November 30, 2023, were $49.7 million and $189.1 million, respectively, compared to $46.1 million and $184.5 million for the three and twelve months ended November 30, 2022, respectively. For the twelve-month period, there was an increase in compensation and related personnel costs and an increase in clinical costs as Nurix continued its clinical trial programs and ongoing patient enrollment, offset by a decrease in research related costs and in contract manufacturing. General and administrative expenses for the three months and twelve months ended November 30, 2023, were $10.8 million and $42.9 million, respectively, compared to $9.4 million and $38.0 million for the three and twelve months ended November 30, 2022, respectively. The increase for the twelve-month period was primarily related to an increase in non-cash stock-based compensation expense and an increase in professional service costs related to the Pfizer collaboration agreement, offset by a decrease in outside consulting costs. Net loss for the three months and twelve months ended November 30, 2023, was $42.0 million or ($0.77) per share and $143.9 million or ($2.65) per share, respectively, compared with $46.7 million or ($0.87) per share and $180.4 million or ($3.71) per share for the three and twelve months ended November 30, 2022, respectively. Cash, cash equivalents and marketable securities was $295.3 million as of November 30, 2023, compared to $268.7 million as of August 31, 2023. About Nurix Therapeutics, Inc. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, 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 cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com. 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 plans and expectations with respect to its current and prospective drug candidates, including its plans to accelerate enrollment in the NX-5948 clinical trial and its expectations with respect to the partial clinical hold on the NX-2127 clinical trial; the tolerability, safety profile, therapeutic potential and other advantages of Nurix’s drug candidates, including their potential to address a range of acquired mutations; the planned timing and conduct of Nurix’s clinical trials; the planned timing for the provision of updates and findings from Nurix’s preclinical studies and clinical trials; the potential benefits of and Nurix’s expectations with respect to its strategic collaborations, including the achievement of research milestones; the potential advantages of Nurix’s scientific approach and DELigase™ platform; and the potential benefits of Fast Track designation. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions regarding the future of Nurix’s business, its 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) whether Nurix will be able to advance its drug candidates, obtain regulatory approval of and ultimately commercialize its drug candidates; (ii) uncertainties related to the timing and results of preclinical studies and clinical trials; (iii) whether Nurix will be able to fund development activities and achieve development goals; (iv) uncertainties related to the timing and receipt of payments from Nurix’s collaboration partners, including milestone payments and royalties on future product sales; (v) the impact of global business, political and macroeconomic conditions, cybersecurity events, instability in the banking system, and global events, including regional conflicts around the world, on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (vi) whether Nurix will be able to protect intellectual property and (vii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Annual Report on Form 10-K for the fiscal year ended November 30, 2023, 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: InvestorsJason Kantor, Ph.D.Nurix Therapeutics, Inc.ir@nurixtx.com Elizabeth Wolffe, Ph.D.Wheelhouse Life Science Advisorslwolffe@wheelhouselsa.com MediaAljanae ReynoldsWheelhouse Life Science Advisorsareynolds@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, 2023 2022 2023 2022Revenue: Collaboration revenue$15,159 $6,783 $56,987 $38,627 License revenue — — 20,000 — Total revenue 15,159 6,783 76,987 38,627 Operating expenses: Research and development 49,713 46,106 189,148 184,497 General and administrative 10,780 9,367 42,902 37,997 Total operating expenses 60,493 55,473 232,050 222,494 Loss from operations (45,334) (48,690) (155,063) (183,867)Interest and other income, net 3,378 1,973 11,115 3,507 Net loss$(41,956) $(46,717) $(143,948) $(180,360)Net loss per share, basic and diluted$(0.77) $(0.87) $(2.65) $(3.71)Weighted-average number of shares outstanding, basic and diluted 54,670,342 53,944,109 54,337,901 48,607,990 Nurix Therapeutics, Inc.Condensed Consolidated Balance Sheets(in thousands)(unaudited) November 30, 2023 2022Assets Current assets: Cash and cash equivalents$54,627 $64,474 Marketable securities, current 233,281 244,667 Prepaid expenses and other current assets 7,595 9,308 Total current assets 295,503 318,449 Marketable securities, non-current 7,421 63,879 Operating lease right-of-use assets 31,142 12,345 Property and equipment, net 16,808 17,163 Restricted cash 901 901 Other assets 3,823 4,022 Total assets$355,598 $416,759 Liabilities and stockholders’ equity Current liabilities: Accounts payable$6,401 $5,064 Accrued expenses and other current liabilities 24,970 22,428 Operating lease liabilities, current 7,489 5,530 Deferred revenue, current 48,098 37,633 Total current liabilities 86,958 70,655 Operating lease liabilities, net of current portion 23,125 6,434 Deferred revenue, net of current portion 45,022 35,974 Total liabilities 155,105 113,063 Stockholders’ equity: Common stock 49 47 Additional paid-in-capital 746,299 709,220 Accumulated other comprehensive loss (655) (4,319)Accumulated deficit (545,200) (401,252)Total stockholders’ equity 200,493 303,696 Total liabilities and stockholders’ equity$355,598 $416,759

Data reveal oncogenic scaffold function of BTK mutations that lack kinase activity and show these mutations remain susceptible to degradation by NX-2127 NX-2127 degrades BTK in patients regardless of mutational status and shows proof-of-concept therapeutic benefit in chronic lymphocytic leukemia Nurix recently presented positive clinical data from ongoing Phase 1 clinical trial of NX-2127 in patients with relapsed/refractory B-cell malignancies at the 65th American Society of Hematology (ASH) Annual Meeting Feb. 01, 2024 -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today announced the publication of a manuscript in the journal Science titled: “Kinase Impaired BTK Mutations Are Susceptible to Clinical Stage BTK and IKZF1/3 Degrader NX-2127” that elucidates a previously unappreciated oncogenic scaffold function of BTK responsible for clinical resistance to enzymatic inhibitors and shows that NX-2127, a potent targeted protein degrader with differentiated activity against BTK and IKZF1/3, can overcome this resistance across a broad range of acquired mutations. “While BTK inhibitors have positively changed clinical outcomes for patients with B-cell malignancies, the emergence of acquired resistance to these medicines is a growing clinical problem,” said Alexey Danilov, M.D., Ph.D. Professor and Co-Director, Toni Stephenson Lymphoma Center, City of Hope National Medical Center. “Identification of the different types of mutations has important implications for the therapeutic sequencing of currently used targeted BTK inhibitors and reinforces the need for the development of novel agents, such as Nurix’s NX-2127 and NX-5948, that have the potential to provide improved mutation-agnostic treatment options for patients.” The article describes studies designed to investigate and characterize acquired BTK mutations that confer resistance to BTK inhibitors commonly used in the treatment of B-cell malignancies. The research identified a new class of kinase impaired mutants that render BTK enzymatically inactive and revealed that these mutations create novel protein-protein interactions that can propagate biochemical signaling through a process known as scaffolding, a nonenzymatic function of the BTK protein that sustains B-cell receptor (BCR) signaling and promotes the growth of malignant B-cells. Importantly, the authors report data demonstrating efficient proteasomal degradation of BTK in the blood of all NX-2127-treated patients with chronic lymphocytic leukemia (CLL), resulting in reduction of BTK enzymatic activity and suppression of BCR signaling regardless of mutational status. The work was carried out by Nurix in collaboration with scientists and clinicians at several prominent cancer research centers, including Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and the Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center. A Drug Annotation manuscript published contemporaneously in The Journal of Medicinal Chemistry entitled “Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton’s Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies” reports data detailing the discovery and optimization of NX-2127, including characterization of NX-2127’s activity in preclinical tumor models, cross-species pharmacokinetics and in vitro safety which supported the advancement of this molecule into clinical testing. “These publications represent the first compendium of biochemical, cellular, and clinical evidence that NX-2127 degrades both previously described and newly discovered BTK inhibitor resistance mutations, a novel mechanism of action in the treatment of B-cell malignancies that is associated with meaningful clinical responses,” said Gwenn M. Hansen, Ph.D., chief scientific officer of Nurix. “The data described in this publication in Science reinforce the broad utility of the targeted protein degradation mechanism compared to inhibition approaches to more completely block BTK function and potentially other important enzymatic disease targets where development of acquired resistance is an issue.” “The first-in-human trial of NX-2127 is ongoing in patients with relapsed and refractory B-cell malignancies, including CLL. Based on our clinic data, which were recently presented at the 2023 ASH Annual Meeting, we have also initiated expansion cohorts in patients with diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL),” said Paula O’Connor, M.D., senior vice president of clinical development at Nurix. “With the ability to target BTK inhibitor resistance mutations and achieve clinical responses, we believe that BTK degraders have the potential to become the next dominant class of agents in the significant BTK-targeted therapy field. We look forward to presenting additional clinical data from this program, and from our NX-5948 BTK degrader program, which is also being evaluated in patients with CLL, at future medical meetings.” NX-2127 is a novel bifunctional, orally bioavailable, investigational new drug that degrades BTK and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137). NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK that, unlike NX-2127, has been designed to lack cereblon immunomodulatory activity. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022). Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative medicines based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions 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 cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com. The content above comes from the network. if any infringement, please contact us to modify.

While any discovery that could lead to new Parkinson’s treatments is “worthy of attention,” the findings must be tempered with “an understanding of the process that follows,” Conscience CEO Ryan Merkely said. An open science competition held by a Canadian nonprofit has announced the discovery of molecules that could someday lead to new treatments for Parkinson’s disease.  In a Jan. 16 press release, the organization, Conscience, said scientists from Merck KGaA, the University of Pittsburgh and elsewhere used artificial intelligence to identify seven commercially-available compounds with novel mechanisms of action against the protein LRRK2, a well-known culprit in inherited Parkinson’s disease. The drugs are the first to show activity against LRRK2’s WD40 repeat (WDR) domain, which is thought to contribute to Parkinson’s toxicity. “Today’s results are a win for open science, for collaboration in drug discovery, as opposed to a patent-driven approach where scientists work in isolation from competing laboratories,” Ryan Merkley, CEO of Conscience, said in the release.  The challenge is the first in a series from a program called the Critical Assessment of Computational Hit-Finding Experiments, or CACHE, which holds a new competition every four months. This one was funded in part by actor Michael J. Fox’s research foundation and was comprised of two rounds: In the first, the 23 participating labs used their own AI algorithms to identify and nominate up to 100 compounds, which were then tested in lab experiments using a series of assays to see how well they bound to the LRRK2 WDR domain. The scientists also tested whether the compounds would bind to unrelated receptors, a sign that they were not specific to LRRK2.  Participants whose compounds showed potential moved on to the second round. They could select up to 50 follow-up compounds, or drugs that had the same mechanisms of action as their original submissions but that might have higher specificity or binding affinity.  CACHE organizers noted on the competition’s website that while they were “generous” in moving compounds from round 1 to round 2—some compounds, for example, were advanced despite having low binding in certain assays or showing activity against an off-target protein—the second round was more stringent.  “The purpose of round 2 is to avoid false positives,” the CACHE team explained on the organization’s site. “Here, we expected to see at least some analogs of the original hit showing some activity.” To ascertain this, they added on additional screenings.  The final data was evaluated by an independent committee made up of industry experts from Astra Zeneca, Bayer, Boehringer Ingelheim, Nuvisan and Relay Therapeutics, CACHE's director Matthieu Schapira confirmed to FBR via email. The top-rated compounds came from the lab of David Koes, Ph.D., at the University of Pittsburgh; Olexander Isayev, Ph.D., and Artem Cherkasov, Ph.D., of Carnegie Mellon and the University of British Columbia, respectively; and Christina Schindler of Merck KGaA. The computational methods of all seven participants who found winning hits can be found on CACHE’s website. While “any discovery that could lead to new treatments” for Parkinson’s is “worthy of attention,” the findings must be tempered with “an understanding of the process that follows,” Merkley told Fierce Biotech Research in an email. The hits are “encouraging starting points for potential development,” he explained, but the compounds will need to undergo much more research before they could even be considered drug candidates.  “We’re excited about these results, but we know what’s next will take time, and nothing is for certain,” he said. “One of the things we hope to see is a more open and honest conversation about the quality and uses of AI tools in drug discovery, and the specific approaches they augment, so we can work to improve them over time.”  Meanwhile, CACHE is now running or gearing up to find new compounds for conditions beyond Parkinson’s. Challenges 2 and 3 seek to find new drugs against COVID-19; challenge 4 asks participants to predict drugs that inhibit the TKB domain of CBLB, a negative regulator of T cell activation that has been linked to lymphoma and is the target of a clinical-stage drug from Nurix Therapeutics. The fifth challenge, which is currently taking applications, aims to identify obesity drugs that target the receptor MCHR1. Editor's Note: This article was updated to clarify that the Michael J. Fox Research Foundation sponsored the first CACHE challenge, not the program as a whole. The names of the pharmaceutical companies whose experts evaluated the final data were also added after publication.