On February 28, 2025 Eli Lilly and Company (NYSE: LLY) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who have been previously treated with a BTK inhibitor (Press release, Eli Lilly, FEB 28, 2025, View Source [SID1234650750]).

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"Results from the BRUIN CLL-321 trial show that Jaypirca delivers clinically meaningful outcomes in a post-BTK inhibitor setting with markedly prolonged time to next treatment, including in those with high-risk characteristics often associated with poor prognosis," said Paolo Ghia, M.D., professor, medical oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy. "Jaypirca allows for continued targeting of the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to be an important new option in a setting with significant unmet need. The CHMP opinion is an important step toward bringing Jaypirca to patients in the European Union."

Following this positive opinion, the application for the use of Jaypirca in patients with relapsed or refractory CLL who have been previously treated with a BTK inhibitor is now referred to the European Commission for final action. The European Commission’s decision is expected in the next one to two months. Jaypirca has also previously received a conditional marketing authorization by the EMA for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have been previously treated with a BTK inhibitor.

The positive opinion is supported by data from the BRUIN CLL-321 clinical trial, the first randomized Phase 3 study in CLL ever conducted exclusively in patients previously treated with a BTK inhibitor. The study’s primary endpoint of progression-free survival (PFS) was met at the prespecified time of final analysis (Aug. 29, 2023), based on independent review committee (IRC) assessment, demonstrating pirtobrutinib was superior to investigator’s choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR), both global standards of care.1 At an updated analysis (Aug. 29, 2024), pirtobrutinib reduced the risk of disease progression or death by 46% compared to IdelaR or BR (median PFS: 14.0 vs. 8.7 months), consistent with the primary analysis. PFS results were consistent across key subgroups, including patients who received prior venetoclax and across subgroups associated with poor prognosis, including those with TP53 mutations and/or 17p deletions, unmutated IGHV status and complex karyotype. Additionally, the median time to next treatment or death (TTNT), a prespecified, descriptive secondary endpoint in the trial that can serve as a surrogate marker for disease control outcomes, was 24 months compared to the control arm of 11 months (63% improvement; HR=0.37 [95% CI, 0.25-0.52]). The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-321 was consistent with safety data from the Phase 1/2 BRUIN study, including adverse events of special interest. The most common adverse reactions of any grade were neutropenia, fatigue, diarrhea, anemia, rash, and contusion.

Results from the BRUIN CLL-321 study were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2024.

"We are pleased to receive a positive opinion from the CHMP, signaling that the European Union may lead the way in broadening patient access to Jaypirca for those with relapsed or refractory CLL in the post-BTK inhibitor setting," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "There are currently no treatment options that have been specifically studied in a randomized Phase 3 trial in this patient population, and we are hopeful Jaypirca will be a meaningful new option for patients. We look forward to the European Commission’s decision in the coming months."

In addition to this positive opinion in CLL and conditional approval in MCL in the EU, Jaypirca was approved in the U.S. in 2023 under the U.S. Food and Drug Administration’s (FDA) Accelerated Approval pathway for the treatment of adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor, and adult patients with CLL or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy including a BTK inhibitor and BCL-2 inhibitor. Lilly has submitted supplemental marketing applications for Jaypirca in the post-BTK inhibitor setting for CLL/SLL patients around the globe, including in the U.S.

About BRUIN CLL-321
BRUIN CLL-321 is a Phase 3, randomized, open-label study of pirtobrutinib versus investigator’s choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in BTK inhibitor pre-treated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The trial enrolled 238 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or investigator’s choice of either IdelaR or BR per labeled doses. This trial’s primary endpoint is progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, as assessed by blinded independent review committee (IRC). Secondary endpoints include PFS, as assessed by investigator; overall response rate (ORR) and duration of response (DoR); event-free survival; overall survival (OS) and time to next treatment (TTNT); safety and tolerability; and patient-reported outcomes (PRO).

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

About Chronic Lymphocytic Leukemia (CLL)
CLL is a form of slow-growing non-Hodgkin lymphoma that develops from white blood cells known as lymphocytes.5,6 CLL is one of the most common types of leukemia in adults.5 There are roughly 100,000 new cases of CLL globally each year, and the overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year.7,8 In CLL, the cancer cells are present in the blood.5

INDICATIONS FOR JAYPIRCA (pirtobrutinib) (in the United States)
Jaypirca is a kinase inhibitor indicated for the treatment of

Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred (4.4%). Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (17%). Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. Upon confirmation of DILI, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.

Most common ARs (≥20%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

PT HCP ISI MCL_CLL AA JUN2024

Please see Prescribing Information and Patient Information for Jaypirca.

On February 28, 2025 Eli Lilly and Company (NYSE: LLY) reported that it will participate in Leerink Partners Global Healthcare Conference on March 10, 2025 (Press release, Eli Lilly, FEB 28, 2025, View Source [SID1234650751]). Lucas Montarce, Lilly executive vice president and chief financial officer, will take part in a fireside chat at 9:20 a.m., Eastern time.

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.

On February 28, 2025 PharmaMar Group (MSE: PHM) reported to have closed fiscal year 2024 with a total revenue of €174.9 million, representing an 11% increase compared to the previous year (Press release, PharmaMar, FEB 28, 2025, View Source [SID1234650753]). Recurring revenue, which includes net sales plus royalties received from partners, grew 3% year-over-year, reaching €127.9 million as of year-end 2024.

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As of December 31st, 2024, total oncology sales amounted to €66.5 million, compared to €70.7 million in the previous year. This difference is due to fluctuations in Yondelis (trabectedin) sales and the reversal of the provision recorded in 2023 on Zepzelca (lurbinectedin) revenue from the compassionate use program in France.

Total lurbinectedin sales in 2024 reached €35.3 million, including revenue from the compassionate use program—mainly in France—of €22.2 million, commercial sales in Europe of €6.4 million, and active ingredient sales of €6.7 million. In comparison, in 2023, total lurbinectedin sales amounted to €36.7 million, a figure that included an accounting adjustment of €10.4 million due to the reversal of a provision for unapplied discounts.
Excluding this adjustment, total lurbinectedin sales in 2024 would have shown an approximate 34% growth.

Total Yondelis revenue in 2024 grew 15%, reaching €54.4 million. This figure includes Yondelis sales, which totaled €31.3 million in 2024 compared to €34.1 million in the previous year, as well as royalties and license agreement revenue, detailed below.

Trabectedin sales include commercial sales in Europe, which reached €18.0 million in 2024, compared to €26.1 million the previous year, and active ingredient sales to partners, which amounted to €13.3 million in 2024, up from €7.9 million in 2023. The increase in active ingredient sales to partners has offset the pricing impact caused by the entry of generics in Europe.

As of December 31st, 2024, PharmaMar Group’s oncology royalty revenue reached €61.3 million, representing an 18% increase compared to the previous year. This growth was driven by royalties received from Jazz Pharmaceuticals for lurbinectedin sales in the U.S., which grew 15% to €55.8 million.

In addition to the royalties received from Jazz Pharmaceuticals through December 31st, 2024, trabectedin royalties from partners in the U.S. and Japan amounted to €5.2 million, representing a 36.4% increase over total trabectedin royalties received in 2023.

Regarding non-recurring revenue from license agreements, as of the end of 2024, this totaled €46.5 million, reflecting a 38.5% increase compared to the previous year. Of this total, €23 million corresponds to deferred revenue recognition from the 2019 agreement with Jazz Pharmaceuticals for lurbinectedin, a similar figure to the previous year. Additionally, €17.9 million came from payments related to the trabectedin license agreement with Janssen (compared to €9.4 million as of December 2023), and €4.4 million corresponded to revenue from the lurbinectedin license agreement with Luye.

PharmaMar Group’s R&D investment in 2024 grew 4% compared to the previous year, reaching €103.5 million.

Of the total R&D investment, the oncology segment saw a 13% increase, reaching €94.4 million. This growth was mainly driven by the advancement of ongoing clinical trials during 2024, such as LAGOON (a Phase III trial for second-line small cell lung cancer treatment) and SaLuDo (a Phase IIb/III trial for leiomyosarcoma treatment). The LAGOON trial completed patient enrolment in the last quarter of 2024.

Additionally, the Company continues investing in the clinical development of early-stage molecules. In this regard, two Phase II clinical trials are ongoing with ecubectedin, along with Phase I trials with PM534 and PM54, all focused on solid tumor treatment.

Thanks to revenue growth in 2024, PharmaMar Group reached an EBITDA of €13.0 million, compared to €2.1 million in 2023.

The Company’s net profit increased to €26.1 million at the end of 2024, compared to €1.1 million in 2023.

As of December 31st, 2024, PharmaMar Group reported a cash and cash equivalents balance of €157 million, with a total financial debt of €47.8 million, reflecting an increase of nearly €8 million compared to the previous year, due to the acquisition of a €15 million long-term bank loan. As a result, the net cash position at the year-end stood at €109 million.

PharmaMar will host a conference call with analysts and investors on February 28th, 2025, at 1:30 PM (CET). To join the conference call, it is recommended to register at this link to receive access numbers and a personalized PIN.

To access the call without prior registration, use the following numbers: +34 919 01 16 44 (Spain), +1 646 233 4753 (USA) o +44 20 3936 2999 (UK). Conference number: 883194.

On February 28, 2025 Recursion (Nasdaq : RXRX) a leading clinical stage TechBio company decoding biology to radically improve lives, reported business updates and financial results for its fourth quarter and fiscal year ended December 31, 2024 (Press release, Recursion Pharmaceuticals, FEB 28, 2025, View Source [SID1234650754]).

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Recursion will host a (L)earnings Call on February 28, 2025 at 8:30 am ET / 6:30 am MT / 1:30 pm GMT from Recursion’s X (formerly Twitter), LinkedIn, and YouTube accounts giving analysts, investors, and the public the opportunity to ask questions of the company by submitting questions here: https://bit.ly/40UiVkb.

"In 2024, Recursion made a transformative leap with the largest TechBio merger in history, combining our pipeline, partnerships, people and platform to further accelerate the Recursion OS as the leading full-stack TechBio platform," said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. "With a portfolio of 10 clinical and preclinical programs, including both potential first-in-class and best-in-class therapies, we are driving towards faster and more effective drug development. These advances position us at the forefront of the next generation of medicine, where the impact will be measured not just in scientific breakthroughs through the power of our platform, but in real-world patient outcomes at scale."

Summary of Business Highlights

Pipeline
pipeline_pgxxa.jpg
1Includes non-small cell lung cancer (NSCLC), colorectal cancer, breast cancer, pancreatic cancer, ovarian cancer, head and neck cancer.
2Joint venture with Rallybio.

•Clinical Results: Recursion demonstrated promising early efficacy data for two programs in 2024
◦REC-617: A potential best-in-class CDK7 inhibitor optimized using our AI platform, delivered early Phase 1/2 results demonstrating promising safety and efficacy, including a durable partial response in a late-stage metastatic ovarian cancer patient and stable disease across four other patients with solid tumors (e.g. CRC, NSCLC). These findings support further clinical development as the Company continues to explore its potential in combination regimens.
◦REC-994: A potential first-in-disease oral superoxide scavenger for symptomatic CCM, showing robust safety in chronic dosing in a Phase 2 study as well as a reduction in lesion volume as measured by MRI and trends towards symptom stabilization as evaluated by mRS. The data was featured in a late-breaking oral presentation at the 2025 International Stroke Conference. Next steps in this program will be informed by regulatory discussions and long-term extension data expected in 2025.
•Clinical Advancements and Regulatory Milestones:
◦Pipeline advanced with the initiation of three new clinical studies:
◦DAHLIA: Phase 1/2 trial investigating REC-1245, a potential first-in-class RBM39 degrader, in biomarker-enriched advanced solid tumors and lymphoma.
◦TUPELO: Phase 1b/2 trial investigating REC-4881 for familial adenomatous polyposis (FAP).
◦ALDER: Phase 2 trial investigating REC-3964, a potential first-in-class C. diff toxin B inhibitor, for preventing recurrent C. difficile infection.
◦Progressed additional programs
◦REC-4359: received IND clearance for REC-4539 (REC-4539 inhibitor) in small cell lung cancer
◦REC-3565: received CTA approval for REC-3565 (MALT1 inhibitor) in b-cell malignancies
◦REC-4209: progressed REC-4209 in idiopathic pulmonary fibrosis to IND-enabling studies

Partnerships

Roche-Genentech:
•Gastrointestinal-Oncology Advancements: In partnership with Roche and Genentech, Recursion has generated multiple whole-genome phenomaps with chemical perturbations across various disease-relevant cell types, enabling deeper insights into how different cellular contexts respond to gene knockouts and chemicals.
•Neuro-specific CRISPR KO Phenomap: In partnership with Roche and Genentech, Recursion developed the first whole-genome CRISPR knockout map in neural iPSC cells, providing valuable data to identify potential new targets in neuroscience, a field which has historically suffered from limited new discoveries.
•Milestones and Collaboration: The neuroscience phenomap work led to the exercise of a $30M option by Roche and Genentech in August 2024, and the collaboration is already moving forward with target validation projects.

Sanofi:
•Immunology & Oncology Achievements: Through this collaboration, Recursion is using its end-to-end integrated platform to discover and advance up to 15 novel targets in the oncology and immunology therapeutic areas.
◦In 2024, two programs advanced through initial milestones, generating $15M in aggregate payments from Sanofi.

Bayer:
•Oncology Achievements: Completed 25 multimodal oncology data packages utilizing the Recursion OS platform. Multiple programs are rapidly progressing to Lead Series nomination.
•LOWE: Additionally, Bayer has adopted Recursion’s LOWE LLM-orchestrated workflow software to enhance their research capabilities.

Merck KGaA (Darmstadt, Germany):
•Ongoing alliance with Merck KGaA, Darmstadt, Germany is focused on leveraging Recursion’s discovery engine to identify first-in-class and best-in-class targets across oncology and immunology, driving innovation in these key therapeutic areas.

Platform

•Full stack AI powered platform: Our constantly-evolving Recursion OS spans target discovery through clinical development, enabling efficient molecule design and testing for both first and best-in-class opportunities.
◦Integration of Exscientia’s Precision Chemistry Platform (Centaur) & Recursion OS:
▪Integrated Centaur into more than 10 design cycles for programs Recursion has previously partnered, with early validation work achieved and progress accelerating across multiple additional partnered programs.
▪The Recursion OS has been used to identify hit compounds in 7 immune-relevant targets or dual target pairs and early validation work has commenced to prepare reports for our partners.
▪Recursion’s AI synthesis planning capability shows a 25% improved tractability assessment of AI-generated compounds over competitors.
◦Compute: Launched BioHive-2, the most powerful supercomputer owned by any biopharma company, enabling the training of industry-leading foundation models like Phenom-2, MolPhenix, and MolGPS.
◦Protein Target Data Layer: Mapped 1.4 million active ligands to binding pockets for structure-based drug discovery and target deconvolution.

◦Phenomics: Scaled phenomics experimental capabilities can now generate up to 16.2 (135 terabytes) million multi-timepoint brightfield images across up to 2.2 million experiments per week.
◦Transcriptomics: Generated >1.6M individual transcriptomes since its launch in 2023, with just under 1M generated in 2024 including building the world’s first genome-scale CRISPR knockout map in primary human cells.
◦Invivomics: Grew dataset to 1 million hours of video; 1 million hours of digital biomarkers and 149,000 environment data points.
◦LLM and Knowledge Graph Integration: Reduced manual effort by 60% for evidence collection for hit nomination packages supporting entry into hit-to-lead through knowledge graphs and LLM-based data aggregation with further reduction expected with additional data layers.
•Breakthroughs in Foundation Models: Developed multimodal AI models like Phenom, MolPhenix, and MolGPS that accelerate Recursion’s ability to make high-confidence predictions in our therapeutics programs.
◦Phenom-2: A 1.9B-parameter model trained on 8B microscopy images, achieving 60% better linear separability of genetic perturbations and top performance in biological relationship recall and consistency.
◦MolPhenix: Delivers a 10X improvement over previous models in predicting the effects of molecules on cell assays and morphology.
◦MolGPS: A 3B-parameter model for molecular property prediction that outperforms the state of the art on 12 of 22 ADMET tasks in the Therapeutic data commons (TDC).
◦MolE: A new foundation model trained on 842M molecular graphs, surpassing earlier approaches by ranking first in 10 ADMET tasks in the TDC.
◦Advancement in Causal AI models & Emerging Focus on ClinTech: Transforming clinical development with Recursion’s ClinTech platform and models, focused on:
◦Utilizing AI models and Tempus data to build a patient stratification framework in small cell lung cancer (SCLC). This work is informing clinical strategies for the planned REC-4539 Phase I study commencing in the first half of 2025.
◦Automating key processes like site engagement and enrollment to accelerate patient matching and industrializing workflows to accelerate trial initiation.
◦Centralizing data systems to optimize clinical protocols, streamline operations, and significantly reduce costs and site burden.

Integration & Additional Corporate Updates

•Recursion completed the combination with Exscientia, becoming an industry-leading TechBio company, bringing together Recursion’s biology-first TechBio platform with Exscientia’s chemistry-first TechBio platform, and creating a compelling set of both first and best-in-class clinical programs and sector-leading partnerships.
•Recursion announced it will carve out its Austrian operations into a newly formed company, Alpha Biotechnology GmbH ("Alpha"). Recursion will have a 49% ownership in Alpha, a company leveraging a patient-tissue platform for the development of precision therapeutics for the treatment of hematological and solid cancers, while focusing its efforts and moderating spend.
•The company is on-track to sub-lease or otherwise simplify its real estate footprint post business combination to concentrate employees in a smaller number of sites while moderating spend.
•Recursion is maintaining its guidance of at least $100 million in synergies from the transaction, with a majority of the run rate amount achieved in 2025.
•The company will provide a comprehensive update in May 2025.

Fourth Quarter and Fiscal Year 2024 Financial Results

Financials reported for the full year 2024 include full year Recursion financials combined with financials from Exscientia post-business combination (November 20-December 31, 2024).

•Cash Position: Cash, cash equivalents and restricted cash were $603.0 million as of December 31, 2024, compared to $401.4 million as of December 31, 2023. On a combined basis, Recursion continues to expect cash runway to extend into 2027.
•Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $4.5 million for the fourth quarter of 2024, compared to $10.9 million for the fourth quarter of 2023. Total revenue, consisting primarily of revenue from collaboration agreements, was $58.8 million for the year ended December 31, 2024, compared to $44.6 million for the year ended December 31, 2023. For the fourth quarter of 2024, the decrease of $6.4 million compared to the prior period was due to the timing of projects from the Company’s Roche and Genentech collaboration. For the year ended December 31, 2024, the increase of $14.3 million compared to the prior year was due to revenue recognized from our Roche and Genentech collaboration related to the completion of Recursion’s first neuroscience phenomap optioned by Roche and Genentech for $30 million.
•Pro Forma Revenue: The Company’s unaudited pro forma consolidated revenue is presented as if the Exscientia business combination had occurred on January 1, 2023. Pro forma revenue was $82.6 million for the year ended December 31, 2024, compared to $72.5 million for the year ended December 31, 2023.
•Research and Development Expenses: Research and development expenses were $98.3 million for the fourth quarter of 2024, compared to $69.5 million for the fourth quarter of 2023. Research and development expenses were $314.4 million for the year ended December 31, 2024, compared to $241.2 million for the year ended December 31, 2023. The increase in 2024 research and development expenses compared to the prior year was driven by our platform and personnel costs as the Company continues to expand and upgrade its platform, including chemical technology, machine learning and transcriptomics platform.
•General and Administrative Expenses: General and administrative expenses were $77.2 million for the fourth quarter of 2024, compared to $30.5 million for the fourth quarter of 2023. General and administrative expenses were $178.2 million for the year ended December 31, 2024, compared to $110.8 million for the year ended December 31, 2023. The increase in 2024 general and administrative expenses compared to the prior year was primarily driven by an increase in salaries and wages of $21.1 million, transaction costs of $20.5 million, inclusion of Exscientia’s results of $11.3 million and increases in software and lease expenses.
•Net Loss: Net loss was $178.9 million for the fourth quarter of 2024, compared to a net loss of $93.0 million for the fourth quarter of 2023. Net loss was $463.7 million for the year ended December 31, 2024, compared to a net loss of $328.1 million for the year ended December 31, 2023.
•Net Cash: Net cash used in operating activities was $115.4 million for the fourth quarter of 2024, compared to net cash used in operating activities of $74.1 million for the fourth quarter of 2023. Net cash used in operating activities was $359.2 million for the year ended December 31, 2024, compared to net cash used in operating activities of $287.8 million for the year ended December 31, 2023. The difference was primarily driven by (1) higher costs incurred for research and development and general and administrative due to Recursion’s expansion and upgraded capabilities and (2) Recursion’s combination with Exscientia.
◦Recursion noted that the change in Exscientia’s cash and cash equivalents and short term bank deposits from December 31, 2023 to November 20, 2024, the date of the close of the acquisition was $184 million. There were no material financings in this period1:

(in thousands) November 20, 2024 December 31, 2023 Change
Cash and cash equivalents $ 277,104 £ 259,463
Short term bank deposits — 103,586
Total – GBP N/A £ 363,049
GBP to USD rate N/A 1.27
Total – USD $ 277,104 $ 461,072 $ (183,968)

On February 28, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending conditional marketing authorization of linvoseltamab to treat adults with relapsed and refractory (R/R) multiple myeloma (MM) (Press release, Regeneron, FEB 28, 2025, View Source [SID1234650755]). The recommendation is specific to those who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. The European Commission is expected to announce a final decision in the coming months.

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The positive CHMP opinion is supported by data from the pivotal LINKER-MM1 trial, which evaluated linvoseltamab in adults with R/R MM. Earlier this month, the FDA accepted for review the Biologics License Application for linvoseltamab. The target action date for the FDA decision is July 10, 2025.

Linvoseltamab is investigational and has not been approved by any regulatory authority.

About Multiple Myeloma
As the second most common blood cancer, there are over 35,000 new cases of MM diagnosed in Europe and 187,000 new cases of MM diagnosed globally every year. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow the progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About the Linvoseltamab Clinical Development Program
Linvoseltamab is an investigational BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in 282 enrolled patients with R/R MM. The Phase 1 dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. The ongoing Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of objective response rate. Key secondary endpoints include duration of response, progression-free survival, rate of minimum residual disease negative status and overall survival.

Eligibility in the Phase 2 portion requires patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. At week 16, all patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve a very good partial response or better and have completed at least 24 weeks of therapy. The regimen requires a total of two 24-hour hospitalizations for safety monitoring.

Linvoseltamab is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. They include evaluating linvoseltamab in a Phase 1b trial (LINKER-MM2) in combination with other cancer treatments in R/R MM as well as a Phase 3 confirmatory trial (LINKER-MM3) as a monotherapy in R/R MM. For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 844-734-6643.