[Translation] A Phase II, Double-Blind, Randomized, Placebo-Controlled Study Followed by an Open-Label Long-Term Extension to Evaluate the Effect of SAR443820 on Serum Neurofilament Protein Levels in Subjects with Multiple Sclerosis

A部分，主要目的：评估 SAR443820 与安慰剂相比对 sNfL 的影响。次要目的：评估 SAR443820 与安慰剂相比对影像学和临床终点的疗效；探索 SAR443820 与安慰剂相比对脑体积和慢性病灶的影响；评估 SAR443820 的安全性和耐受性；评估 SAR443820 的药代动力学（PK）。B部分，主要目的：评估 sNfL 持久时间的长期趋势。次要目的：探索 SAR443820 对脑体积和慢性病灶的影响；评估 SAR443820 的长期安全性和耐受性；评估 SAR443820 对疾病进展和活动的长期影响，通过其他身体功能相关临床和影像学指标及患者报告结局（PRO）评估。

[Translation]

Part A, primary objective: To evaluate the effect of SAR443820 on sNfL compared with placebo. Secondary objectives: To evaluate the efficacy of SAR443820 on imaging and clinical endpoints compared with placebo; To explore the effect of SAR443820 on brain volume and chronic lesions compared with placebo; To evaluate the safety and tolerability of SAR443820; To evaluate the pharmacokinetics (PK) of SAR443820. Part B, primary objective: To evaluate the long-term trend of sNfL persistence. Secondary objectives: To explore the effect of SAR443820 on brain volume and chronic lesions; To evaluate the long-term safety and tolerability of SAR443820; To evaluate the long-term effect of SAR443820 on disease progression and activity, as assessed by other physical function-related clinical and imaging indicators and patient-reported outcomes (PROs).

Start Date04 Jan 2023

Sponsor / Collaborator

Sanofi-Aventis Recherche et Développement SA

[+1]

NCT05630547 / Active, not recruitingPhase 2

A Phase 2 Double-blind, Randomized, Placebo-controlled Study Evaluating the Effect of SAR443820 on Serum Neurofilament Levels in Participants With Multiple Sclerosis, Followed by an Open-label Long-term Extension Period

This is a Phase 2, randomized, double-blind, placebo-controlled 2 parallel-arm study to assess the effect on serum neurofilament light chain (sNfL), safety and tolerability of oral SAR443820 compared to placebo in male and female participants aged 18 to 60 years with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) (relapsing or non-relapsing), or primary progressive multiple sclerosis (PPMS) followed by an open-label long-term extension period.
The total study duration is approximately 100 weeks and includes the following:
4-week screening period 48-week double-blind treatment period (Part A) 48-week open-label long-term extension period (Part B)

Start Date19 Dec 2022

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Oditrasertib

100 Translational Medicine associated with Oditrasertib

100 Patents (Medical) associated with Oditrasertib

Literatures (Medical) associated with Oditrasertib

01 Jan 2024·Clinical and Translational Science

Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants

Article

Author: Eastenson, Amy ; Pomponio, Robert ; Atassi, Nazem ; Ofengeim, Dimitry ; Nicolas, Xavier ; Hsiao-Nakamoto, Jennifer ; Krupka, Emmanuel ; Cantalloube, Cathy ; Lewanczyk, Pascale ; Hincelin-Mery, Agnes ; Benamor, Myriam

AbstractSAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor‐interacting serine/threonine protein kinase 1 (RIPK1). This phase I first‐in‐human healthy participant study (NCT05795907) was comprised of three parts: randomized, double‐blind, placebo‐controlled single ascending dose (SAD; part 1a); 14‐day multiple ascending dose (MAD; part 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SAR443820; and a separate open‐label, single‐dose part 1b (PK‐cerebrospinal fluid [CSF]) to assess SAR443820 levels in CSF. SAR443820 was well‐tolerated in healthy participants, and no treatment discontinuation related to an adverse event (AE) occurred. Most common AEs were dizziness and headache. No clinically meaningful changes were noted in laboratory values, vital signs, or electrocardiogram parameters. SAR443820 had a favorable PK profile, with plasma half‐lives (geometric mean) ranged between 5.7–8.0 h and 7.2–8.9 h after single and repeated doses, respectively. There were no major deviations from dose proportionality for maximum concentration and area under the curve across SAR443820 doses. Mean CSF‐to‐unbound plasma concentration ratio ranged from 0.8 to 1.3 over time (assessed up to 10 h postdose), indicating high brain penetrance. High levels of inhibition of activated RIPK1, as measured by decrease in pS166‐RIPK1, were achieved in both SAD and MAD parts, with a maximum median inhibition from baseline close to 90% at predose (Ctrough) after multiple dosing in MAD, reflecting a marked RIPK1 target engagement at the peripheral level. These results support further development of SAR443820 in phase II trials in amyotrophic lateral sclerosis (NCT05237284) and multiple sclerosis (NCT05630547).

News (Medical) associated with Oditrasertib

06 Nov 2024

·www.globenewswire.com

Denali Therapeutics Reports Third Quarter 2024 Financial Results and Business Highlights

SOUTH SAN FRANCISCO, Calif., Nov. 06, 2024 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the third quarter ended September 30, 2024, and provided business highlights. "As leaders in pioneering a new class of therapeutics that cross the blood-brain barrier, we are making significant progress across our Transport Vehicle (TV)-enabled portfolio,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “Within our Enzyme TV (ETV) franchise, we are on track to file for accelerated approval of tividenofusp alfa in MPS II in early 2025 after a successful meeting with the FDA in the third quarter. Today, we are also pleased to share that preliminary data from our Phase 1/2 study of DNL126 in MPS IIIA demonstrate a robust reduction from baseline in CSF heparan sulfate levels, including normalization. Based on these data and a positive regulatory environment, we recently expanded the study to support a potential accelerated path. In addition, our recent preclinical publication on our oligonucleotide TV (OTV) technology in Science Translational Medicine, which describes broad and deep brain biodistribution of oligonucleotides following systemic administration of OTV, demonstrates the power and potential of our TV platform to transform the way we treat brain diseases.” Third Quarter 2024 and Recent Program Updates Late-stage and mid-stage clinical programs Tividenofusp alfa (DNL310): Enzyme Transport Vehicle (ETV)-enabled, iduronate-2-sulfatase (IDS) replacement therapy in development for MPS II (Hunter syndrome) In September, announced the outcome of a successful meeting with the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA) providing a path to filing a biologics license application (BLA) for accelerated approval and subsequent conversion to full approval for tividenofusp alfa (DNL310) for the treatment of MPS II. Agreement was reached that cerebrospinal fluid heparan sulfate (CSF HS) is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support accelerated approval for tividenofusp alfa in MPS II. Denali intends to submit the BLA under the accelerated approval pathway in early 2025.In September, presented new interim data from the Phase 1/2 study at the Society for the Study of Inborn Errors of Metabolism (SSIEM 2024), including data from additional study participants (N=37) and longer duration of treatment with tividenofusp alfa (up to Week 129) as well as new analyses on biomarkers and clinical outcomes.COMPASS, the global Phase 2/3 study, is expected to complete enrollment in 2024. DNL343: eIF2B activator in development for the treatment of amyotrophic lateral sclerosis (ALS) DNL343 is being evaluated in Regimen G (DNL343) of the Phase 2/3 HEALEY ALS Platform Trial conducted by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) in collaboration with the Northeast ALS Consortium (NEALS). Enrollment in Regimen G is complete. SAR443820/DNL788: CNS-penetrant RIPK1 inhibitor In October, Denali was informed by its strategic partner Sanofi that the K2 Phase 2 study evaluating the safety and efficacy of oditrasertib (SAR443820/DNL788) on serum neurofilament light chain levels in participants with multiple sclerosis was discontinued based on not meeting the primary and key secondary endpoints. BIIB122/DNL151: LRRK2 inhibitor in development for the treatment of Parkinson’s disease (PD) Biogen is conducting the ongoing global Phase 2b LUMA study of BIIB122 in participants with early-stage Parkinson’s disease.Denali has initiated screening of participants for the global Phase 2a study to evaluate safety and biomarkers associated with BIIB122 in participants with Parkinson’s disease and confirmed pathogenic variants of LRRK2. This study is being funded under the Collaboration and Development Funding Agreement with a third party. Eclitasertib (SAR443122/DNL758): Peripheral RIPK1 inhibitor in development for the treatment of ulcerative colitis (UC) Sanofi is conducting the ongoing Phase 2 study of SAR443122/DNL758 in participants with UC. Early-stage clinical and preclinical programs DNL126: ETV-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy in development for the treatment of MPS IIIA (Sanfilippo syndrome Type A) Denali today announced that preliminary data from up to 25 weeks of dosing in the ongoing open-label Phase 1/2 study in MPS IIIA participants demonstrate a significant reduction in CSF HS levels from baseline, including normalization. The safety profile supports continued development. The most frequent treatment emergent adverse events were infusion related reactions of mild and moderate severity in all participants. There was one serious adverse event considered by the investigator not related to drug. Denali plans to present the data at a future medical meeting.Based on the preliminary Phase 1/2 results and a positive regulatory environment, Denali recently expanded the study and continues to assess the development plans including an accelerated approval path.DNL126 was selected in June 2024 for the FDA's Support for clinical Trials Advancing Rare disease Therapeutics (START) program to accelerate the development of rare disease therapeutics, and collaborative engagement has commenced to support progress to a pre-BLA meeting. TAK-594/DNL593: Protein Transport Vehicle (PTV)-enabled progranulin (PGRN) replacement therapy in development for the treatment of frontotemporal dementia-granulin (FTD-GRN) Screening of participants for Cohort B2 in the Phase 1/2 study is ongoing. Oligonucleotide Transport Vehicle (OTV) platform Denali is advancing OTV:MAPT, targeting tau for Alzheimer’s disease, and OTV:SNCA, targeting alpha-synuclein for Parkinson’s disease, in the investigational new drug (IND)-enabling stage of development.In August, announced publication of nonclinical data in the August 14, 2024 issue of Science Translational Medicine (link) demonstrating the ability of the OTV platform to achieve broad biodistribution of antisense oligonucleotides (ASOs) in the central nervous system and skeletal and cardiac muscle following intravenous administration. Antibody Transport Vehicle Amyloid beta (ATV:Abeta) program Denali is working to develop the next generation of anti-amyloid beta therapeutics with ATV:Abeta, which is designed to increase exposure of the therapeutic antibody and achieve broad biodistribution in the brain with the potential for improved efficacy and safety. Preclinical data demonstrated potential for a wider therapeutic window compared to a standard antibody, with superior plaque decoration and reduction and very low rates of amyloid related imaging abnormalities (ARIA). These data are included in a manuscript posted on bioRxiv (link).Denali plans to advance a TfR-targeting ATV:Abeta molecule as well as a CD98hc-targeting ATV:Abeta molecule into development for Alzheimer's disease. Discovery programs Denali applies its deep scientific expertise in neurodegeneration biology and the BBB to discover and develop medicines and platforms with the focus on programs enabled by the TV technology and targeting neurodegenerative disease, including Alzheimer’s and Parkinson’s, and lysosomal storage diseases. 2024 Guidance on Operating Expenses Cash, cash equivalents, and marketable securities were approximately $1.28 billion as of September 30, 2024. Denali is providing updated guidance on cash operating expenses for the full year 2024 and now anticipates an increase of approximately 5-10% compared to 2023, which is an increase from previous guidance of equal to or less than full year 2023 cash operating expenses. This updated guidance is associated with increased activities to support filing of a BLA in early 2025 and commercial readiness for tividenofusp alfa in MPS II, and to accelerate the development of additional therapeutic programs in Denali's TV platform portfolio. Participation in Upcoming Investor Conferences UBS Global Healthcare Conference, November 11-14B. Riley Securities’ Next-Gen Tissue Delivery Modalities Virtual Summit, November 14Stifel 2024 Healthcare Conference, November 18-19Jefferies London Healthcare Conference, November 19-217th Annual Evercore ISI HealthCONx Conference, December 3-5 Third Quarter 2024 Financial Results Net losses were $107.2 million and $99.4 million for the three months ended September 30, 2024 and 2023, respectively. There was no collaboration revenue for the quarter ended September 30, 2024, compared to $1.3 million for the quarter ended September 30, 2023. The decrease in collaboration revenue was primarily due to activities under the Biogen Collaboration Agreement. Total research and development expenses were $98.2 million for the quarter ended September 30, 2024, compared to $89.7 million for the quarter ended September 30, 2023. The increase of approximately $8.5 million for the quarter ended September 30, 2024 was primarily attributable to increases in costs in various clinical stage programs, including ETV:IDS, eIF2B, ETV:SGSH, and LRRK2 reflecting the continued progress of these programs in clinical trials, and increases in TV platform and other program external expenses, reflecting continued investment in TV-enabled product candidates. These increases were partially offset by a decrease in personnel and external expenses associated with the divestiture of Denali’s preclinical small molecule programs. General and administrative expenses were $24.9 million for the quarter ended September 30, 2024, and $25.3 million for the same period in 2023. About Denali Therapeutics Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB, and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding expectations regarding Denali’s TV technology platform; statements made by Denali’s Chief Executive Officer; plans, timelines, and expectations regarding DNL310 and the ongoing Phase 2/3 COMPASS and Phase 1/2 studies, the timing and likelihood of accelerated approval, and the timing and availability of program updates; plans and timelines regarding DNL343, including the timing and availability of data from the Phase 2/3 HEALEY ALS Platform Trial; plans, timelines, and expectations of both Denali and Sanofi regarding DNL788; plans, timelines, and expectations regarding DNL151, including with respect to the ongoing LUMA study as well as enrollment and timing of the proposed Phase 2a study in PD patients with LRRK2 mutations; expectations regarding DNL758, including the ongoing Phase 2 study in patients with UC; plans, timelines, and expectations related to DNL126, including the timing and availability of data in the ongoing Phase 1/2 study and the timing and likelihood of regulatory approval; plans, timelines, and expectations of both Denali and Takeda regarding DNL593 and the ongoing Phase 1/2 study; plans, timelines, and expectations regarding the advancement of OTV:MAPT and OTV:SNCA towards clinical development; plans, timelines, and expectations regarding the ATV:Abeta program, including its therapeutic potential and the clinical advancement of ATV:Abeta molecules; plans and expectations for Denali's preclinical programs; Denali's future operating expenses and anticipated cash runway; and Denali's participation in upcoming investor conferences. All drugs currently being developed by Denali are investigational and have not received regulatory approval for any indication. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: any and all risks to Denali’s business and operations caused by adverse economic conditions; risk of the occurrence of any event, change, or other circumstance that could give rise to the termination of Denali’s agreements with Sanofi, Takeda, or Biogen, or any of Denali’s other collaboration agreements; Denali’s transition to a late-stage clinical drug development company; Denali’s and its collaborators’ ability to complete the development and, if approved, commercialization of its product candidates; Denali’s and its collaborators’ ability to enroll patients in its ongoing and future clinical trials; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials; Denali’s dependence on successful development of its blood-brain barrier platform technology and its programs and product candidates; Denali’s and its collaborators' ability to conduct or complete clinical trials on expected timelines; the risk that preclinical profiles of Denali’s product candidates may not translate in clinical trials; the potential for clinical trials to differ from preclinical, early clinical, preliminary or expected results; the risk of significant adverse events, toxicities or other undesirable side effects; the uncertainty that product candidates will receive regulatory approval necessary to be commercialized; Denali’s ability to continue to create a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 28, 2024 and August 1, 2024, respectively, and Denali’s future reports to be filed with the SEC. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results, or to make changes in Denali’s expectations, except as required by law. Denali Therapeutics Inc.Condensed Consolidated Statements of Operations(Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Collaboration revenue: Collaboration revenue from customers(1)$— $1,267 $— $330,531 Other collaboration revenue — — — — Total collaboration revenue — 1,267 — 330,531 Operating expenses: Research and development(2) 98,238 89,737 296,653 316,073 General and administrative 24,949 25,325 75,379 78,585 Total operating expenses 123,187 115,062 372,032 394,658 Gain from divestiture of small molecule programs — — 14,537 — Loss from operations (123,187) (113,795) (357,495) (64,127)Interest and other income, net 15,995 14,442 49,475 38,376 Net loss$(107,192) $(99,353) $(308,020) $(25,751)Net loss per share, basic and diluted$(0.63) $(0.72) $(1.89) $(0.19)Weighted average number of shares outstanding, basic and diluted 169,456,988 137,644,534 162,589,325 137,076,199 __________________________________________________ (1) Includes related-party collaboration revenue from customers of $1.3 million and $295.5 million for the three and nine months ended September 30, 2023, respectively.(2) Includes expenses for cost sharing payments due to a related party of $3.4 million and $14.5 million for the three and nine months ended September 30, 2023, respectively. Denali Therapeutics Inc.Condensed Consolidated Balance Sheets(Unaudited)(In thousands) September 30, 2024 December 31, 2023Assets Current assets: Cash and cash equivalents$90,636 $127,106Short-term marketable securities 745,923 907,405Prepaid expenses and other current assets 32,280 29,626Total current assets 868,839 1,064,137Long-term marketable securities 445,463 —Property and equipment, net 50,822 45,589Operating lease right-of-use asset 23,717 26,048Finance lease right-of-use asset 38,685 —Other non-current assets 26,487 18,143Total assets$1,454,013 $1,153,917Liabilities and stockholders' equity Current liabilities: Accounts payable$9,594 $9,483Accrued clinical and other research & development costs 23,923 19,035Accrued manufacturing costs 9,568 15,462Accrued compensation 14,874 21,590Operating lease liability, current 8,036 7,260Deferred research and development funding liability, current 16,269 —Other accrued costs and current liabilities 4,829 5,152Total current liabilities 87,093 77,982Operating lease liability, less current portion 38,850 44,981Finance lease liability, less current portion 5,631 —Deferred research funding and development liability, less current portion 3,944 —Total liabilities 135,518 122,963Total stockholders' equity 1,318,495 1,030,954Total liabilities and stockholders’ equity$1,454,013 $1,153,917 Investor Contact:Laura Hansen, Ph.D.Vice President, Investor Relationshansen@dnli.com(650) 452-2747 Media Contact:Rich AllanFGS Global Rich.Allan@fgsglobal.com(503) 851-0807

Phase 2Financial StatementAccelerated Approval

15 Oct 2024

·www.outsourcing-pharma.com

Sanofi abandons phase 2 trial of Denali’s multiple sclerosis candidate

The K2 trial tested oditrasertib’s safety and ability to reduce the blood levels of neurofilament light chain, a biomarker of neuronal damage in multiple sclerosis. However, the trial failed to meet its primary and undisclosed key secondary endpoints, according to a filing . Multiple sclerosis is a degenerative and progressive disorder where the immune system attacks the insulation around nerve cells, leading to the death of the cells and to increasing disability in people with the condition, which number around 2.8 million . Oditrasertib is designed to block a protein called receptor-interacting protein kinase 1 (RIPK1), which is involved in cell death. Blocking RIPK1 could make nerve cells more resistant to the pathology and slow down the disease. Denali obtained oditrasertib in 2016 when it took over the previous developer Incro Pharmaceuticals. Sanofi then got in on the action when it inked a $1 billion strategic collaboration with Denali in 2018 to develop candidates for the treatment of immunological and neurological conditions. Numerous setbacks The partnership has faced numerous obstacles in the last few years. Another of the RIPK1 inhibitors in the deal flopped in a phase 1b trial for the treatment of Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) in 2020, leading the partners to focus on oditrasertib. In February this year, however, oditrasertib failed in a phase 2 trial for the treatment of ALS and Sanofi discontinued the trial. Another RIPK1 inhibitor in the sights of the partners is eclitasertib, which cannot penetrate the central nervous system and is in phase 2 development for the treatment of ulcerative colitis. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Denali Therapeutics raised $500 million in a private placement in February this year and its main candidate, an enzyme replacement therapy to treat the rare disease mucopolysaccharidosis type II, is in a phase 2/3 trial set to complete enrollment this year. The growing prevalence of multiple sclerosis is set to drive the global market for treatments, which was worth $21.3 billion in 2023 and is projected to grow by 7.9% to $38.9 billion by 2032. Getting a RIPK1 blocker to the market is proving difficult for many players, with a candidate developed by GlaxoSmithKline showing no efficacy signs in clinical results in patients with ulcerative colitis published in 2021. Some of the most advanced RIPK1 contenders include phase 1-stage programs by China’s GenFleet Therapeutics, Roche’s U.S. company Genentech, and a compound developed by Eli Lilly and Rigel Pharmaceuticals.

Phase 2Drug ApprovalPhase 1Acquisition

11 Oct 2024

·www.biopharmadive.com

FDA clears Roche breast cancer drug; Turnstone lays off 60% of staff

Today, a brief rundown of news from Roche and Turnstone Biologics, as well as updates from Sanofi, Pfizer and Flagship Pioneering that you may have missed.Turnstone Biologics will lay off about 60% of its workforce and trim its pipeline in a bid to focus on a cancer cell therapy program in human testing, the company announced Friday. Through the restructuring, Turnstone will deprioritize preclinical work and put resources into a cell therapy in a Phase 1 trial for a variety of solid tumors. An update on the study is expected next year, while the restructuring moves will enable Turnstone to operate through the second quarter of 2026. Turnstoneraised $80 million in an initial public offering last year, but shares have lost nearly all of their value since. Ben FidlerThe Food and Drug Administration on Thursday approved a new Roche drug for breast cancer.Called Itovebi, the drug has been cleared for use with PfizersIbrance and endocrine therapy in people whose HR-positive, HER2-negative breast tumors have a mutation called PIK3CA. Itll compete for market share with Novartis Piqray, another medicine targeting PIK3CA mutations.Itovebi is one of five drugs Roche aims to add to its portfolio of breast cancer treatments, which already includes the targeted therapies Herceptin, Perjeta and Kadcyla. Jonathan GardnerVaccine developer Gritstone bio has filed for bankruptcy. The company said Thursday its in discussions with a party that would act as a potential buyer or plan sponsor, and should have some kind of deal ironed out as early as next week. The disclosure comes just weeks after Gritstone tapped the investment bank Raymond James to be its financial adviser as the biotech evaluated potential value-maximizing strategies. Earlier this year, the company laid off a significant portion of its employees and, shortly after, received disappointing results from a key study of its experimental vaccine for colorectal cancer. Jacob BellDenali Therapeuticssaid in a regulatory filingThursday that partner Sanofi has stopped a Phase 2 trial testing one of the biotechs experimental drugs in multiple sclerosis after the therapy missed its main and secondary study goals. The drug, oditrasertib, is part of a broad partnership Denali and Sanofi signed in 2018 to develop treatments for autoimmune and neurological diseases. It previously failed a study in ALS. Delilah AlvaradoA dual regimen of PfizersTalzenna and Xtandi helped people with advanced prostate cancer live longer than those who received Xtandi alone in a clinical trial, regardless of whether they had certain genetic alterations believed to be associated with a stronger benefit, the company said Thursday. The FDA last year approved the Talzenna-Xtandi combinationonly for people with these genetic signatures because of concerns over the safety and effectiveness of so-called PARP inhibitors like Talzenna in a broader population. Its issued similarly narrow clearances to Merck & Co. and AstraZenecas Lynparza and Johnson & Johnsons Akeega. With the new results, though, Pfizer now seeks to expand use of Talzenna. Jonathan GardnerPaul Parker is joining Flagship Pioneering as a managing partner, where hell oversee the biotechnology startup creators fundraising activities and manage its relationships with investors, the firm announced Thursday. Parker, who who previously served in top roles within the mergers and acquisitions groups of Goldman Sachs, Barclays Group and Lehman Brothers, is now Flagships third managing partner along with Doug Cole and Stephen Berenson. His appointment comes three months after Flagship raised $3.6 billion in additional capital and announced more than a dozen promotions and new hires to its leadership team. Gwendolyn WuThe FDA has turned back an experimental hypoglycemia drug from Zealand Pharma for the second time in less than a year. In a statement Tuesday, Zealand said the agency didnt approve the therapy, dasiglucagon, because of the timing related to the re-inspection of a third-party manufacturing facility. An initial examination of the facility uncovered deficiencies unrelated to Zealands drug, but nonetheless led the FDA to reject dasiglucagon in December. The re-inspection took place in August and September, but the manufacturer, which Zealand didnt name, hasnt yet received a positive recommendation. Delilah Alvarado '

Drug ApprovalClinical ResultVaccinePhase 1Executive Change

100 Deals associated with Oditrasertib

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Preclinical	US	Sanofi-Aventis Recherche et Développement SA	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	JP	Sanofi (China) Investment Co. Ltd.	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	DE	Sanofi	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	NL	Sanofi	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	CN	Sanofi	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	BE	Sanofi	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	JP	Sanofi-Aventis Recherche et Développement SA	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	IT	Sanofi (China) Investment Co. Ltd.	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	PL	Sanofi	13 Apr 2022
Amyotrophic Lateral Sclerosis	Preclinical	IT	Sanofi-Aventis Recherche et Développement SA	13 Apr 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05237284 (HIMALAYA, Biospace) Manual	Phase 2	Amyotrophic Lateral Sclerosis	-	SAR443820	(mcfjfxhgdt) = did not meet kilffkqolq (dflesydvov ) Not Met	Negative	19 Feb 2024

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