On October 7, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, reported preclinical findings for its SHP2 inhibitor, BBP-398, in non-small cell lung cancer (NSCLC) (Press release, BridgeBio, OCT 7, 2021, View Source [SID1234590923]). The results are featured in a poster presentation titled ‘BBP-398, a potent, small molecule inhibitor of SHP2, enhances the response of established NSCLC xenografts to KRASG12C and EGFRmut inhibitors’ at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) taking place virtually on October 7 – 10, 2021.

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"We are excited to share our promising preclinical data in non-small cell lung cancer models, which provides a critical step in understanding the potential that BBP-398 has for patients with tumors driven by RAS or other MAPK-pathway activating mutations," said Eli Wallace, Ph.D., chief scientific officer at BridgeBio Oncology. "For patients with this type of progressive cancer, there is a serious need for more innovative medicines to be accessible as quickly as possible. Our potentially best-in-class SHP2 inhibitor could be an ideal combination agent for certain cancer patients given its promising profile of preclinical results and potential for once daily dosing."

BBP-398, developed in collaboration with the University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division, exhibits preclinical monotherapy efficacy in RTK/KRAS-driven xenograft models as well as synergy in combination with both sotorasib and osimertinib. The predicted human steady-state plasma concentration-time profiles suggest continuous once daily oral dosing of BBP-398 may achieve the desired therapeutic index for patients.

BridgeBio is currently advancing its Phase 1 dose escalation clinical trial with its SHP2 inhibitor, BBP-398, in patients with solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes. More than 30% of all human cancers – including 95% of pancreatic cancers and 45% of colorectal cancers — are driven by mutations of the RAS family of genes.

BridgeBio’s precision oncology programs are driven by the Company’s molecular dynamics and RAS structural biology platforms, which are enabled by our broad partnerships with the Lawrence Livermore National Laboratory and National RAS Initiative, respectively.

BridgeBio’s SHP2 inhibitor, BBP-398, is one of the Company’s 14 programs that are in the clinic or commercial setting for patients living with genetic diseases and genetically-driven cancers.

Learn more about the preclinical data for BBP-398 at BridgeBio’s upcoming virtual R&D Day on Tuesday, October 12, 2021 at 8:30 am ET. The event will be webcast and registration information can be found here.

BridgeBio will unveil new programs, share new information about its pipeline and discuss how it is broadening the scope of its R&D engine. It will also cover the Company’s most significant near-term catalysts with a focus on the upcoming topline results for acoramidis, BridgeBio’s investigational therapy for transthyretin (TTR) amyloidosis (ATTR). ATTR is a rare heart condition with a progressive and debilitating impact on quality of life likely affecting more than 400,000 patients worldwide.

Topline acoramidis results from Part A are expected in late 2021 and from Part B in 2023. The primary endpoint at Part A is the change from baseline in a 6-minute walk distance (6MWD) in trial participants receiving acoramidis or placebo after 12 months. If the change from baseline in 6MWD in Part A is highly statistically significant, BridgeBio expects to submit an application for regulatory approval of acoramidis in 2022 to the U.S. Food and Drug Administration.

The R&D Day program importantly and additionally will highlight BridgeBio’s broader efforts in cardiorenal, progress in its KRAS portfolio, and advancements in its previously disclosed early-stage Mendelian programs. The Company will also be unveiling new investigational programs in gene therapy.

About SHP2
SHP2 is a protein-tyrosine phosphatase that links growth factor, cytokine and integrin signaling with the downstream RAS/ERK MAPK pathway to regulate cellular proliferation and survival. Overactivity of the SHP2 pathway, often driven by distinct genetic mutations, is a critical contributor to many forms of cancer, and is a mechanism of resistance to several targeted therapies. Estimated to affect approximately 500,000 patients in the United States and the European Union, cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations such as KRASG12C, may be sensitive to SHP2 inhibition.

About BBP-398
BBP-398 is a potent, selective, orally bioavailable SHP2 inhibitor that demonstrates pathway inhibition across a panel of cell lines with active MAPK signaling. The therapy is designed to be optimized for continuous once daily dosing through its pharmacokinetic profile. The inhibitor was developed through a collaboration with the University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division. BridgeBio has a non-exclusive, co-funded clinical collaboration with Bristol Myers Squibb to evaluate the combination of BBP-398 with OPDIVO (nivolumab) in patients with advanced solid tumors with KRAS mutations. The collaboration will also include the initiation of a Phase 1/2 study to evaluate the safety and preliminary efficacy of BBP-398 in combination with both OPDIVO as doublet therapy, and OPDIVO plus a KRASG12C inhibitor as triplet therapy in non-small cell lung cancer (NSCLC) with KRAS mutations, as first- and second-line treatment options. Additionally, BridgeBio previously entered into a strategic collaboration with LianBio for clinical development and commercialization of BBP-398 in combination with various agents in solid tumors such as non-small cell lung cancer, colorectal and pancreatic cancer, in mainland China and other major Asian markets.

On October 7, 2021 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported the presentation of preclinical data demonstrating the synergistic impact of poziotinib when combined with KRAS inhibitors in KRASG12C mutant specific cell lines (Press release, Spectrum Pharmaceuticals, OCT 7, 2021, View Source [SID1234590922]). Jacqulyne Robichaux, Ph.D., Assistant Professor, University of Texas, MD Anderson Cancer Center is presenting a poster titled "Pan-ErbB inhibition enhances activity of KRASG12C inhibitors in preclinical models of KRASG12C mutant cancers" at the Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) being held October 7-10. The conference is hosted by the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute (NCI), and the European Organization for Research and Treatment of Cancer (EORTC).

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The preclinical data demonstrated that inhibition of EGFR, HER2, HER3, and HER4 signaling by the pan-ErbB inhibitor poziotinib was synergistic when combined with KRASG12C inhibitors. These results highlight the importance of HER3 and HER4 signaling, in addition to EGFR and HER2, after KRASG12C inhibition.

"We are encouraged by these promising data developed by Dr. John Heymach and the research team at MD Anderson," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "The in vitro findings presented by Dr. Robichaux illustrate well the importance of pan-HER inhibition blocking the over expression of HER receptors induced by KRAS inhibitors. Poziotinib is a potent clinical stage pan-HER inhibitor and may be optimally suited for this rational combination. These exciting findings warrant further evaluation in the clinic given the large number of patients with NSCLC and other solid tumors with KRASG12C mutations who could possibly benefit from such a combination."

The poster presentation will be available for viewing by registered participants during the conference via the meeting website beginning at 9 a.m. ET on October 7, 2021. It will also be available on the Spectrum Pharmaceuticals website at: View Source

On October 7, 2021 Amgen (NASDAQ: AMGN) reported new combination study results from the Phase 1b CodeBreaK 101 study, a comprehensive global master protocol trial evaluating the safety and efficacy of LUMAKRAS (sotorasib), the first and only approved KRASG12C inhibitor, in more than 10 different investigational combination regimens for the treatment of patients with KRAS G12C-mutated cancers (Press release, Amgen, OCT 7, 2021, View Source [SID1234590921]). Results from two arms of the study — LUMAKRAS with afatinib, a pan-ErbB tyrosine kinase inhibitor, and LUMAKRAS with trametinib, a mitogen-activated protein kinase inhibitor (MEKi) — will be presented at the plenary session titled ‘Drugging Difficult Targets’ during the AACR (Free AACR Whitepaper)-NCI-EORTC 2021 Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on Saturday, Oct. 9, 2021.

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"A critical component of cancer drug development is to interrogate multiple pathways to understand whether different combinations can meaningfully advance cancer care. For this reason, Amgen has undertaken the broadest and most comprehensive global clinical development program for patients with the KRAS G12C mutation, exploring multiple combinations that will allow us to understand where we can best serve patients," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Consistent with our master protocol clinical trial design, which allows us to rapidly add, expand or remove cohorts to quickly understand what combinations work best for patients, Amgen will take these afatinib and trametinib results into account as we prioritize which combinations to move forward within our comprehensive LUMAKRAS development program. We look forward to presenting additional data, including PD-1 and SHP2 combination datasets, in the coming months."

LUMAKRAS in Combination with Afatinib (Abstract LBA6581)
The LUMAKRAS and afatinib combination arm enrolled 33 heavily pre-treated patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC), including five patients previously treated with LUMAKRAS monotherapy. Ten patients received 20 mg of afatinib/960 mg of sotorasib (cohort 1; 4 patients with prior LUMAKRAS experience) and 23 patients received 30 mg of afatinib/960 mg of sotorasib (cohort 2; 1 patient with prior LUMAKRAS experience). The objective response rate (ORR) was 20% in cohort 1 and 35% in cohort 2, and the disease control rate was 70% and 74% in the two cohorts, respectively.

The most common treatment-related adverse events (TRAEs) for this study were diarrhea, nausea, and vomiting. TRAEs of grade 3 occurred in 30% of patients in both dose groups with diarrhea being the most common.

LUMAKRAS in Combination with Trametinib (Abstract LBA6580)
In CodeBreaK 101, the combination of LUMAKRAS and trametinib showed antitumor activity in heavily pre-treated patients with KRAS G12C-mutated solid tumors, including those with prior KRASG12C inhibitor treatment. A total of 41 patients were enrolled in the Phase 1b study with 18 patients with NSCLC, 18 patients with colorectal cancer (CRC) and five patients with other solid tumors. The maximum tolerated dose tested was 2 mg trametinib/960 mg sotorasib administered daily.

In patients with CRC who were KRASG12C inhibitor naïve, 9% achieved partial response (1 of 11), and 82% achieved disease control (9 of 11). In patients who were previously treated with a KRASG12C inhibitor, 14% achieved partial response (1 of 7), and 86% achieved disease control (6 of 7).

In patients with NSCLC who were KRASG12C inhibitor naïve, 20% achieved partial response (3 of 15) and 87% achieved disease control (13 of 15). In patients who were previously treated with a KRASG12C inhibitor, 67% achieved disease control (2 of 3).

The most common TRAEs for this study were diarrhea, rash, dermatitis acneiform, nausea and vomiting. No new safety concerns were identified.

About LUMAKRASTM (sotorasib)
Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS, a KRASG12C inhibitor.1 LUMAKRAS has demonstrated a positive benefit-risk profile with rapid, deep and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.2

In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval anywhere in the world with its approval in the U.S., under accelerated approval. LUMAKRAS is also approved in the United Arab Emirates, and in Canada and Great Britain under Project Orbis.

Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, including triplets, with clinical trial sites spanning five continents. To date, LUMAKRAS has treated over 3,000 patients around the world through the clinical development program and commercial use.

In the U.S., LUMAKRAS was reviewed by the FDA under its Real-Time Oncology Review (RTOR), a pilot program that aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Amgen is participating in the FDA’s Project Orbis initiative and through the initiative, has Marketing Authorization Applications (MAAs) for sotorasib in review in Australia and Brazil. Additionally, Amgen has submitted an MAA in the European Union, Japan, Switzerland, South Korea, Singapore, Israel, Turkey, Taiwan, Colombia, Thailand, Mexico and Hong Kong.

LUMAKRAS is also being studied in multiple other solid tumors.1

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline. The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been submitted for publication.

A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) has completed enrollment. Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).

For information, please visit www.hcp.codebreaktrials.com.

LUMAKRASTM (sotorasib) U.S. Indication
LUMAKRASTM is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS (sotorasib) Important Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.
Please see LUMAKRASTM full Prescribing Information.

About Amgen Oncology
At Amgen Oncology, our mission to serve patients drives all that we do. That’s why we’re relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we’re advancing oncology at the speed of life.

For more information, follow us on www.twitter.com/amgenoncology.

On October 7, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that nonclinical data describing the expression of fibroblast activating protein (FAP) in a variety of solid tumor types will be presented during the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 7-10, 2021 (Press release, Clovis Oncology, OCT 7, 2021, View Source [SID1234590920]). The analysis, conducted with its partner 3B Pharmaceuticals GmbH, measured FAP expression in multiple tumor types using immunohistochemistry (IHC) as well as the correlation between FAP expression by IHC and in vitro binding of FAP-2286, Clovis’ peptide-targeted radionuclide therapy (PTRT) clinical development candidate that targets FAP.

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"We believe these findings across multiple solid tumor types demonstrate the importance of FAP as a cancer target and underscore the potential for 177Lu-FAP-2286 to treat patients with FAP-expressing tumors," said Dr. Thomas Harding, Executive Vice President and Chief Scientific Officer of Clovis Oncology. "These provide additional validation for our ongoing Phase 1/2 LuMIERE clinical trial of FAP-2286, the first peptide-targeted radionuclide therapeutic in clinical development targeting FAP, and support investigation of FAP-2286 in a broad number of cancer indications. This is representative ofour commitment to emerge as a leader in targeted radionuclide therapy by developing innovative radiotherapies such as FAP-2286 for patients with hard-to-treat cancers."

To determine FAP protein expression in different tumor types, a pan-tumor IHC screen was performed that included 360 samples representing 16 different tumor types. For this analysis, high FAP expression was defined as an overall H-score ≥30 in more than 30% of the samples analyzed in a given tumor type. The IHC screen showed high FAP expression in nine of the 16 solid tumor types evaluated, including pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade.

The analysis also demonstrated that in most tumor types, FAP expression was predominantly localized to the stroma surrounding the tumor cells within the tumor microenvironment. FAP expression in tumor cells was also observed: in cancers of mesenchymal origin, such as sarcoma and mesothelioma, tumor-cell expression was common, consistent, and strong; in cancers of epithelial origin, tumor-cell FAP expression was rare and, when present, appeared weaker than in the adjacent stroma.

A significant correlation was seen between FAP expression observed by IHC and in vitro FAP-2286 binding as determined by autoradiography, suggesting that FAP is an attractive target for PTRT in a wide array of tumor types.

Following are details of the Clovis-sponsored presentation:

Poster Number: LBA032 – Pan-Cancer Analysis of Fibroblast Activation Protein Alpha (FAP) Expression to Guide Tumor Selection for the Peptide-Targeted Radionuclide Therapy FAP-2286

Lead author: Tanya T. Kwan, PhD

Category: Radiotherapeutics

Date/Time: Thursday, October 7 at 9:00 am ET

The presentation and accompanying poster can also be viewed at: View Source

For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program CLICK HERE.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use.High FAP expression has been shown in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors (NCT04939610). The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

On October 7, 2021 Recursion (NASDAQ: RXRX), a clinical-stage biotechnology company decoding biology by integrating technological innovations across biology, chemistry, automation, machine learning and engineering, reported that the U.S. Food and Drug Administration (FDA) has granted the company Fast Track designation for the investigation of REC-2282 for treatment of patients with NF2-mutated meningiomas, including neurofibromatosis type-2 disease-related meningiomas (Press release, Recursion Pharmaceuticals, OCT 7, 2021, View Source [SID1234590918]). REC-2282 is a potentially first-in-class, orally bioavailable, CNS-penetrant small molecule HDAC inhibitor being developed for the treatment of NF2-mutated meningiomas.

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The FDA’s Fast Track designation was established to expedite the review of investigational drugs to treat serious conditions and address unmet medical needs by enabling important drugs to get to patients earlier if approved. Fast Track designation can lead to more frequent interactions with the FDA, as well as Accelerated Approval and/or Priority Review eligibility if certain criteria are met.

"The Fast Track designation for REC-2282 is an important addition to our work to develop this medicine to treat patients with neurofibromatosis type-2 and patients with sporadic meningiomas driven by mutations in the NF2 gene, for which there is a significant unmet need," said Recursion Chief Medical Officer Ramona Doyle, M.D. "I am pleased that the team continues to advance this important medicine towards a Phase 2/3, randomized, multi-center study in patients with NF2-mutated meningiomas, for which we expect to begin enrollment early next year."

Meningiomas are primary tumors of the meninges of the central nervous system. More than 34,000 patients are diagnosed with sporadic meningiomas in the US each year. In patients with progressive meningiomas, more than a third are driven by mutations in the gene NF2. NF2-mutated meningiomas are typically treated with surgery and radiotherapy or with off-label therapies of limited or unproven efficacy. The lack of approved therapies to prevent progression of NF2-mutated meningiomas, which are frequently an aggressive tumor type, represents a significant unmet medical need. In addition, the syndrome neurofibromatosis type-2, which is associated with both sporadic and autosomal dominant inherited mutations in the NF2 gene, gives rise to meningiomas in approximately half of neurofibromatosis type-2 patients. In the US and EU5, neurofibromatosis type-2 affects approximately 33,000 patients and there are no approved therapies.