On June 13, 2025 Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics, reported updated, positive data from the Phase 1 ENABLE clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia (CML) in an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress taking place June 12-15 in Milan, Italy, and virtually (Press release, Enliven Therapeutics, JUN 13, 2025, View Source [SID1234653888]).

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"Thanks to the success of tyrosine kinase inhibitors (TKIs), patients with CML now have a near-normal life expectancy. As a result, treatment goals have evolved beyond response and survival to also prioritize quality of life and tolerability," said Andreas Hochhaus, Professor of Internal Medicine, Hematology and Oncology and Head of the Department of Hematology and Medical Oncology at the Jena University Hospital, Germany. "However, significant unmet needs remain, particularly related to treatment resistance and intolerance, across all lines of therapy. The data from ELVN-001 are encouraging, showing an efficacy, safety and tolerability profile that compare favorably to approved BCR::ABL1 inhibitors, despite being studied in a more heavily pretreated population. I look forward to future data, which could support ELVN-001 as a promising new option for patients who need better long-term disease management."

"We are highly encouraged by the ELVN-001 data, specifically as it relates to the consistency of the cumulative and achieved MMR rates as the Phase 1 trial progresses, with more evaluable patients and longer duration of treatment," said Helen Collins, M.D., Chief Medical Officer of Enliven. "While MMR is the efficacy endpoint in CML, safety and tolerability are equally critical given the chronic nature of the disease. ELVN-001 was reported to be well tolerated across all evaluated doses and had low levels of dose reductions and discontinuations, which we believe is the key sign of a favorable safety and tolerability profile. We believe ELVN-001 has the potential to offer best-in-class efficacy and tolerability, which are key attributes for people living with CML. We look forward to sharing additional data in the future."

ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion, the oncogenic driver for patients with CML.

ELVN-001 Data Highlights

Patient Demographics

As of the cutoff date of April 28, 2025, 90 patients have been enrolled in the ongoing Phase 1 trial across dose levels ranging from 10 mg once a day (QD) to 80 mg twice a day (BID).
The vast majority of patients (80%) remain on study with a median treatment duration of ~29 weeks.
Patients enrolled were heavily pretreated:
67% of patients received three or more unique prior TKIs, including 58% of patients who received prior asciminib and 43% of patients who received prior ponatinib.
72% of patients had discontinued their prior TKI due to lack of efficacy.
Encouraging ELVN-001 Efficacy Data by 24 Weeks

Of the enrolled patients, 53 with typical BCR::ABL1 transcripts and without T315I mutations were evaluable for major molecular response (MMR) by 24 weeks.
25 of 53 (47%) evaluable patients were in MMR by 24 weeks, with 13 of 41 (32%) achieving and 12 of 12 (100%) maintaining MMR.
Of those resistant to their last TKI, 14 of 34 (41%) were in MMR by 24 weeks.
Of those previously treated with asciminib or ponatinib, 12 of 34 (35%) were in MMR by 24 weeks.
All patients who achieved or maintained MMR were still in MMR at the time of data cutoff.
These data continued to compare favorably to precedent Phase 1 MMRs for approved BCR::ABL1 TKIs, particularly given the more heavily pretreated patient population in the ELVN-001 clinical trial.
Specifically, the achieved MMR rate by 24 weeks of 32% compares favorably with historical data from less heavily pretreated patients receiving asciminib, which showed achieved MMR rates of 24% in the Phase 1 trial and 25% in the ASCEMBL Phase 3 trial.
ELVN-001’s Safety Profile Consistent with High Selectivity for ABL1

ELVN-001 remains well-tolerated across all evaluated doses.
Only 3.4% (3 of 87) of patients had dose reductions due to treatment-emergent adverse events (TEAEs) and 4.6% (4 of 87) of patients discontinued due to TEAEs.
The majority of TEAEs were low frequency and low grade, and the hematologic TEAE profile was similar to or better than the approved TKIs.
Only 2.3% (2 of 87) of patients experienced ≥ Grade 3 non-hematologic treatment-related AEs.
No evidence to date of enhanced cardiovascular toxicity and no treatment-related arterial occlusive events (AOEs).
The maximum tolerated dose was not reached, and no exposure-toxicity relationship was observed.
ELVN-001 Pharmacokinetic (PK) Profile

The PK profile supports once-daily dosing with flexible administration requirements, including the ability to take with or without food.
There is low potential for drug-drug interactions, an important advantage given that the average CML patient takes approximately five concurrent medications.
"We believe there remains significant opportunity to improve upon existing therapies," said Sam Kintz, Co-founder and Chief Executive Officer of Enliven. "Based on today’s encouraging Phase 1 update, we believe ELVN-001 has the potential to compete across all lines of therapy. We believe that precedent registrational trials in CML provide a roadmap for the regulatory pathway for ELVN-001, and the use of biomarker-based endpoints, like MMR, enables smaller, faster studies. Importantly, historical Phase 1 data in late-line CML trials have predicted success in subsequent pivotal trials. Building off this exciting update, we expect to initiate our first head-to-head Phase 3 pivotal trial in 2026 and remain confident in ELVN-001 and its potential positioning in the future in the CML treatment paradigm."

The oral presentation titled: "ENABLE: A Phase 1a/1b Study of ELVN-001, a selective active site inhibitor of BCR::ABL1, in patients with previously treated CML" will be presented by Andreas Hochhaus, Professor of Internal Medicine, Hematology and Oncology and Head of the Department of Hematology and Medical Oncology at the Jena University Hospital, Germany later today. A copy of the presentation will be available on the "Program Presentations & Publications" section of the Company’s website at www.enliventherapeutics.com.

Webcast and Conference Call Information
Enliven will host a live webcast and conference call today at 1:30 p.m. ET / 7:30 p.m. CEST. To participate in the live event, please register using this link. Following registration, participants will have access to dial in numbers and a unique passcode should they prefer to participate by phone. The event and accompanying slides can also be accessed by visiting the investor relations section of the Company’s website at View Source An archived webcast will be available on the Company’s website following the event.

About the ENABLE Trial
The ENABLE study (NCT05304377) is a Phase 1 study of ELVN-001 in patients with previously treated CML. The trial is currently in Phase 1a/1b development and is a dose escalation and expansion trial designed to evaluate safety and tolerability and to determine the recommended dose for further clinical evaluation of ELVN-001 in patients with CML with and without T315I mutations that is relapsed, refractory or intolerant to TKIs. Secondary endpoints include pharmacokinetics, MMR by central quantitative reverse transcriptase polymerase chain reaction, duration of MMR, BCR::ABL1 transcript levels and complete hematologic response. Enliven is preparing for the potential start of a pivotal trial for ELVN-001 in 2026.

About ELVN-001
ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion, the oncogenic driver for patients with chronic myeloid leukemia. As a highly selective active site inhibitor, ELVN-001 has a mechanism of action that is complementary to allosteric BCR::ABL1 inhibitors, which may play an increasingly important role in the standard of care. ELVN-001 was also designed to have activity against the T315I mutation, the most common BCR::ABL1 mutation, which confers resistance to nearly all approved TKIs, as well as activity against mutations known to confer resistance to allosteric BCR::ABL1 inhibitors.

On June 13, 2025 FDA approved an IND application enabling Myrio’s lead product (PHOX2B PC-CAR T) to enter human trials (Press release, Myrio Therapeutics, JUN 13, 2025, View Source;drug-administration-fda-approves-investigational-new-drug-ind-application-for-myrios-lead-product-phox2b-pc-car-t-for-the-treatment-of-neuroblastoma-302480916.html [SID1234653887]). Myrio, in collaboration the leading children’s hospital in Philadelphia have co-developed a Chimeric Antigen Receptor (CAR-T) therapy for the treatment of neuroblastoma. Under the leadership of Prof. John Maris, a functionally relevant and highly specific protein, called PHOX2B, was identified in neuroblastoma cells and the team elucidated that a peptide from PHOX2B could serve as an excellent target for an immunotherapy to treat this devastating disease.

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Myrio developed a highly specific binder to the PHOX2B peptide-major histocompatibility complex (p-HLA) target using its unique ReDTM technology. In collaboration with the hospital, the Myrio binder has been engineered into a CAR-T product. Importantly, unlike other binders which target a single HLA-allotype, Myrio’s binder is capable of recognizing the peptide in multiple HLA-allotypes, a phenomenon referred to as breaking HLA restriction, which offers the opportunity to treat a broader population of patients using the same immunotherapy.

This groundbreaking approach was detailed in a publication by Myrio, in the journal Nature titled "Targeting of intracellular oncoproteins with peptide-centric CARs."[1] in November 2023.

This is the first time a binder developed by Myrio will enter a human trial and is a major validation of the company’s technology, building on the significant insights shared in their joint research.

"Neuroblastoma is the most common tumor of the sympathetic nervous system, the most common malignancy of infancy and accounts for 15% of pediatric cancer-related deaths", said Prof. Maris. The current treatment options for patients with high-risk neuroblastoma are associated with low response rates and significant toxicities and the development of new treatment options is desperately needed. This investigational immunotherapy has the potential to be a major advance for patients suffering from this devastating disease".

The Phase 1 clinical trial entitled "PHOX2B Peptide-Centric Chimeric Antigen Receptor Autologous T cells (PHOX2B PC-CAR T) for Relapsed Neuroblastoma will be conducted under the leadership of Prof. Maris and it is anticipated that the first patient will be enrolled mid-year 2025.

Dr Graeme Wald, CEO of Myrio Therapeutics commented "that this is a major step forward for Myrio. It is the culmination of many years of work at Myrio in developing bispecific binders to Human Leukocyte Antigens for the treatment of solid tumours."

About Neuroblastoma

Neuroblastoma is the most common tumor of the sympathetic nervous system (97%) and the most common malignancy of infancy with a median age of diagnosis of 17 months.[2] The annual incidence of neuroblastoma in the United States is approximately 800 cases, and it accounts for 15% of pediatric cancer-related deaths.3 Due to the high variability in its presentation, clinical signs and symptoms at presentation can range from a benign palpable mass with distension to major illness from substantial tumor spread. Although overall increases in five-year event-free survival have been reported, this has come at the cost of significant life threating treatment-related side effects, and subgroup-specific analysis of mortality has revealed discordance between the high cure rates for the more benign low-risk forms and little improvement in the high-risk groups.

On June 13, 2025 Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics, reported that it has priced its previously announced underwritten public offering of 8,394,737 shares of its common stock at a price to the public of $19.66 per share and, in lieu of common stock to investors who so choose, pre-funded warrants to purchase up to 1,780,263 shares of Enliven’s common stock at a price to the public of $19.659 per pre-funded warrant, which represents the per share public offering price of each share of Enliven’s common stock less the $0.001 per share exercise price for each pre-funded warrant (Press release, Enliven Therapeutics, JUN 13, 2025, View Source [SID1234653886]). All of the shares and pre-funded warrants are being sold by Enliven. The gross proceeds from the offering are expected to be approximately $200 million before deducting underwriting discounts and commissions and other offering expenses. The offering is expected to close on or about June 16, 2025, subject to satisfaction of customary closing conditions. In addition, Enliven has granted the underwriters a 30-day option to purchase up to an additional 1,526,250 shares of its common stock at the public offering price, less the underwriting discounts and commissions.

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Jefferies, Goldman Sachs & Co. LLC, TD Cowen and Mizuho are acting as joint book-running managers for the offering. LifeSci Capital is acting as lead manager for the offering.

The offering is being made pursuant to a Registration Statement on Form S-3, including a base prospectus, previously filed with and declared effective by the SEC and a related registration statement that was filed with the SEC on June 13, 2025 pursuant to Rule 462(b) under the Securities Act of 1933, as amended (and became automatically effective upon filing), and Enliven has filed with the SEC a preliminary prospectus supplement and accompanying prospectus relating to the offering. A final prospectus supplement and accompanying prospectus relating to the offering will also be filed with the SEC. These documents can be accessed for free through the SEC’s website at www.sec.gov. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained from: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, or by telephone at (877) 821-7388, or by email at [email protected]; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, or by email at [email protected]; TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, NY 10017, by telephone at (833) 297-2926 or by email at [email protected]; or Mizuho Securities USA LLC, Attention: Equity Capital Markets, 1271 Avenue of the Americas, 3rd Floor, New York, NY 10020, by telephone at (212) 205-7600 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful before registration or qualification under the securities laws of any such state or jurisdiction.

On June 13, 2025 Johnson & Johnson (NYSE: JNJ) reported the first clinical data from an ongoing Phase 1b study for JNJ-90014496 (JNJ-4496), an investigational dual-targeting anti-CD19/CD20 bispecific autologous chimeric antigen receptor (CAR) T-cell therapy, being studied in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) who have not been previously treated with CAR T-cell therapy (Press release, Johnson & Johnson, JUN 13, 2025, View Source;johnsons-dual-targeting-car-t-cell-therapy-shows-encouraging-first-results-in-large-b-cell-lymphoma-302480701.html [SID1234653885]). Findings demonstrate the potential of JNJ-4496 in the treatment of patients with R/R LBCL, including R/R diffuse large B-cell lymphoma (DLBCL) – the most common type of aggressive lymphoma, a blood cancer that originates in the lymphatic system.1,2 These data were presented as an oral presentation at the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Congress (Abstract #S239).1

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JNJ-4496, formerly known as C-CAR039, is a dual-targeting CAR T designed to bind to both CD19 and CD20 antigens — two cell surface proteins commonly expressed on malignant B-cells. This design, including a 4-1BB costimulatory domain, is intended to enhance binding strength and persistence, also potentially addressing common mechanisms of resistance in relapsed or refractory disease.

In the Phase 1b dose confirmation study (NCT05421663) in patients with R/R LBCL, data at the recommended Phase 2 dose (RP2D) were reported in patients with a median follow-up of 4 months. Results informed a RP2D of JNJ-4496 at 75 million CAR+ T-cells. Among the 22 patients in the RP2D group where efficacy was assessed, those who received one prior line of therapy (n=10) had an objective response rate (ORR) of 100 percent and a complete response rate (CRR) of 80 percent (95 percent confidence interval (CI), 69, 100). In the patients who had received two or more prior lines of therapy (n=12), the ORR was 92 percent and the CRR was 75 percent (95 percent CI, 62, 100).1

"There is a pressing need to continue advancing therapies for patients with relapsed or refractory diffuse large B-cell lymphoma. Only about 40 percent of patients have long-term remissions with currently available single-antigen-targeting CD19 CAR T therapies," said Krish Patel*, M.D., Director of Lymphoma Research, Sarah Cannon Research Institute (SCRI), and principal study investigator. "The data presented today show encouraging clinical activity and promising safety, and represent a step forward in delivering a potential new treatment option to patients living with the most common type of aggressive lymphoma."

Within the RP2D safety group (n=25), 52 percent of patients (n=13) received two or more prior lines of therapy, and 56 percent (n=14) received bridging therapy. In the RP2D cohort studied, no cases of Grade 3 or 4 cytokine release syndrome were observed. Two patients had immune effector cell-associated neurotoxicity syndrome (ICANS), one Grade 1 and one Grade 3. The Grade 3 event occurred in a patient with central nervous system (CNS) lymphoma. Overall, 84 percent of patients (n=21) had Grade 3/4 treatment-emergent adverse events (TEAEs), and 28 percent (n=7) reported serious TEAEs. The most common Grade 3/4 TEAE was neutropenia, a reduction in white blood cells (72 percent). One patient experienced a Grade 3 infection.1

"We’re really excited to share the first results for our dual-targeting anti-CD19/CD20 CAR T-cell therapy in relapsed or refractory large B-cell lymphoma, underscoring our more than decade-long commitment to addressing unmet needs for patients with B-cell malignancies," said Jeffrey Infante, M.D., Vice President of Early Clinical Development and Translational Research at Johnson & Johnson Innovative Medicine. "As we continue to unlock the full potential of CAR T-cell therapies through novel next-generation approaches, these promising data reinforce earlier long-term findings and highlight the potential of JNJ-4496 to improve outcomes for patients."

These data are advancing our pipeline of CAR T therapies for the treatment of B-cell malignancies and are an extension of our worldwide collaboration and licensing agreement initiated with AbelZeta Inc. (formerly Cellular Biomedicine Group, Inc.) in 2023 to develop and commercialize next-generation CAR T-cell therapies (excluding Greater China). A Phase 1 study for C-CAR039 was conducted in China for the treatment of patients with B-cell non-Hodgkin lymphoma (predominantly LBCL).3 Johnson & Johnson is also evaluating the safety and efficacy of this asset (known as JNJ-4496 outside of Greater China) through a separate study involving a global patient population.4 In addition to the oral presentation of JNJ-4496 at EHA (Free EHA Whitepaper), the global clinical study data will be presented at the 2025 International Conference on Malignant Lymphoma from June 17—21.

About large B-cell lymphoma
Large B-cell lymphoma is a type of non-Hodgkin lymphoma (NHL), a blood cancer that originates in the lymphatic system, arising from abnormal B cells, a type of white blood cell responsible for producing antibodies to fight infections.2 The malignant cells grow rapidly in lymph nodes or other organs and can spread quickly throughout the body.2 These abnormal cells are larger than normal, healthy B-cells.2 Diffuse (D) LBCL is the most common and aggressive type where cells are spread out (diffuse) rather than grouped together when they are examined under a microscope.2 DLBCL accounts for approximately 40 percent of all NHL cases globally and is estimated to have 150,000 new cases diagnosed each year.5 While some patients respond to initial treatment, up to 40 percent can relapse or become refractory to therapy.6 LBCL and DLBCL patients often face limited treatment options and a poor prognosis, highlighting the urgent need for innovative therapies. Common symptoms include rapidly growing lymph nodes, fever, night sweats, weight loss, and fatigue.

On June 13, 2025 AstraZeneca reported to have entered a strategic research collaboration with Shijiazhuang City-based CSPC Pharmaceuticals Group Limited (Press release, AstraZeneca, JUN 13, 2025, View Source [SID1234653884]). Working together on high priority targets, the collaboration aims to advance the discovery and development of novel oral candidates, with the potential to treat diseases across multiple indications.

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Under the terms of the agreement, AstraZeneca and CSPC agree to discover and develop pre-clinical candidates for multiple targets with the potential to treat diseases across chronic indications, including a pre-clinical small molecule oral therapy for immunological diseases.

Sharon Barr, Executive Vice President and Head of BioPharmaceuticals R&D said: "This strategic research collaboration underscores our commitment to innovation to tackle chronic diseases which impact over two billion people globally. Forming strong collaborations allows us to leverage our complementary scientific expertise to support the rapid discovery of high-quality novel therapeutic molecules to deliver the next-generation medicines."

The research will be carried out by CSPC, in Shijiazhuang City and will utilise their AI-driven, dual-engine efficient drug discovery platform. This platform uses AI technology to analyse the binding patterns of target proteins with existing compound molecules, conduct targeted optimization, with the aim of selecting highly effective small molecules with excellent developability.

The collaboration furthers AstraZeneca’s presence in China following the $2.5bn investment in Beijing announced earlier this year and strengthens the ongoing collaboration with CSPC.

Financial considerations
Under the terms of the agreement, CSPC will receive an upfront payment of $110 million, and is also eligible to receive up to $1.62 billion in potential development milestone payments and up to $3.6 billion in sales milestone payments, plus potential single digit royalties based on annual net sales of the products.

Under the agreement, AstraZeneca will have rights to exercise options for exclusive licenses to develop and commercialise worldwide candidates identified under this agreement.