On September 16, 2025 Researchers at Children’s Hospital of Philadelphia (CHOP) reported a novel antibody-drug conjugate (ADC) that shows striking efficacy against cancers that express the anaplastic lymphoma kinase (ALK) protein on the cancer cell surface (Press release, CHOP, SEP 16, 2025, View Source [SID1234656009]). The therapy, named CDX0239-PBD, achieved complete and lasting tumor responses in preclinical models of neuroblastoma, rhabdomyosarcoma and colorectal carcinoma, according to findings published in Nature Communications. The breakthrough could unlock a new class of precision medicine treatments for both childhood and adult cancers, potentially improving short- and long-term patient outcomes and minimizing the harmful side effects of many current treatments.

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Yael P. Mossé, MD, Professor of Pediatrics and leader of the Neuroblastoma Developmental Therapeutics Program at CHOP’s Cancer Center, and her team are renowned for the groundbreaking discovery of gain-of-function mutations in the ALK gene, which are the primary cause of hereditary neuroblastoma and the most common mutations in its sporadic forms. This discovery was pivotal as it identifies ALK as the only mutated oncogene in neuroblastoma that can be targeted for therapy, reducing the likelihood of toxic side effects. The new research, an outgrowth of Mossé’s work, was led by Alberto D. Guerra, MD, PhD, a fellow within the Division of Oncology at CHOP.

In the study, researchers combined CDX0239, a humanized antibody targeting ALK, with a potent chemotherapy agent called pyrrolobenzodiazepine (PBD) dimer. This innovative approach directs the antibody to cancer cells, delivering the chemotherapy inside to kill cancerous cells while mostly sparing healthy ones that do not express ALK. The ADC remained stable in the bloodstream, an essential step for moving the research into human trials.

"Our findings represent an important advance in the field of antibody-drug conjugates for pediatric solid tumors, an area where progress has lagged," said Guerra. "By combining tumor selectivity with potent drug delivery, CDX0239-PBD offers a potential blueprint for future pediatric solid tumor therapies."

The therapy’s effectiveness is closely linked to ALK levels on the surface of cancer cells. Those with a range of ALK surface expression responded well, even when expression was modest. This is particularly exciting as these findings credential the opportunity to leverage an ADC approach for a broad population of patients. In preclinical studies with human tumor models, three total weekly doses of CDX0239-PBD successfully eliminated tumors, resulting in 100% survival across several highly drug-resistant preclinical models. The effects were seen not only in pediatric cancers like neuroblastoma and rhabdomyosarcoma but also in colorectal carcinoma, underscoring the treatment’s potential versatility.

The therapy also achieved success where others did not. For example, in models resistant to lorlatinib, an FDA-approved ALK inhibitor, and those with TP53 mutations and MYCN amplification, treatment with CDX0239-PBD led to lasting positive effects and complete survival. Molecular analyses confirmed that the treatment caused DNA damage and activated cell-death pathways inside tumors, validating its mechanism of action to be selective delivery of a potent chemotherapy drug to cancer cells expressing ALK, and likely also to neighboring tumor cells which may not necessarily express ALK, a phenomenon referred to as the "bystander effect."

Moving forward, the research team is working on refining the technology to meet strict regulatory requirements for developing a first-in-class ALK-directed ADC, aiming for first-in-human/first-in-children early phase clinical trial testing within the next two years. The team is also exploring alternative antibodies with features that would allow for better penetration into the solid tumor microenvironment.

"Precision medicine is transforming our approach to cancer treatment by moving beyond one-size-fits-all therapies," said Mossé. "By tailoring treatments to the unique characteristics of each tumor, we can specifically target cancer cells, thereby increasing the potency and reducing harmful side effects on healthy cells. Our hope is to significantly boost survival rates for patients fighting aggressive cancers while also enhancing their quality-of-life post-treatment."

This work was supported in part by the National Cancer Institute grants (R01CA140198-11-1, R37CA282041 and K08CA230223), Patricia Brophy Endowed Chair in Neuroblastoma Research, DOD Award (W81XWH-12-1-0486), the National Institutes of Health grant (R013208130624), the National Institutes of Health grant (DP2HD108775), funding from Braden’s Hope Foundation, the Margaret Q Landenberger Foundation, NIH Grant (2T32CA009615) and the Howard Hughes Medical Institute (HHMI).

On September 16, 2025 K36 Therapeutics, Inc. ("K36"), a privately held clinical-stage biotechnology company developing novel, targeted therapies for cancers with unmet medical need, reported a clinical update on its lead asset, KTX-1001 for multiple myeloma (MM) (Press release, K36 Therapeutics, SEP 16, 2025, View Source [SID1234656007]).

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The company has initiated patient dosing in an expansion cohort evaluating KTX-1001, its first-in-class NSD2/MMSET inhibitor, in combination with carfilzomib and dexamethasone (NCT05651932). NSD2 (also known as MMSET) is overexpressed in MM patients with the t(4;14) chromosomal translocation, one of the highest-risk genetic subtypes of the disease.

In addition, K36 has begun dosing patients in a separate cohort evaluating KTX-1001 in combination with mezigdomide, a novel investigational therapy from Bristol Myers Squibb (BMS) currently completing enrollment in two pivotal late-stage trials. To enable this study, the companies have entered into a clinical trial supply agreement, under which K36 will sponsor and run the trial to evaluate the novel triplet of KTX-1001, mezigdomide and dexamethasone in patients with relapsed and refractory MM (EUCTR: 2022-500801-41-00). K36 retains all development and commercial rights to KTX-1001 and is free to expand its use in other agents.

"We are excited to see the dose expansion cohorts open in the U.S. and EU and to see continued momentum for KTX-1001, an oral therapy we believe holds great promise to transform outcomes in multiple myeloma," said Terry Connolly, Ph.D., President and Chief Executive Officer of K36. "Despite advances that have extended survival for people living with MM, this challenging blood cancer remains incurable, and most patients eventually relapse. There is an urgent need for therapies that are both effective and convenient, enabling patients to receive care in community settings while also maintaining quality of life. We are deeply grateful to the patients, investigators, and their care teams for their commitment to advancing this important research. The favorable tolerability profile of KTX-1001, together with promising early signs of clinical activity, underscores its potential as a first-in-class targeted therapy for patients with t(4;14) multiple myeloma, and our agreement with BMS enables us to further explore its potential benefit in novel combinations."

"The combination of KTX-1001 with mezigdomide represents an exciting therapeutic opportunity for patients with high-risk t(4;14) multiple myeloma," said Dr. María-Victoria Mateos, MD, PhD, Director of the Myeloma Program and the Clinical Trials Unit in Salamanca’s University Hospital and Associate Professor of Medicine at the University of Salamanca, Spain. "This cohort builds on compelling preclinical evidence showing that KTX-1001 works synergistically with mezigdomide. With the first patient now dosed in this novel-novel cohort, we are encouraged by the potential of this approach to improve outcomes."

K36-MMSET Phase 1 Clinical Trial Details

K36 has opened all U.S. sites for its Phase 1 trial evaluating the safety and tolerability of KTX-1001 in combination with standard of care agents, as well as a novel combination with mezigdomide in Spain and France. The trial’s primary objectives are to determine the provisional recommended Phase 2 dose (RP2D) for these combinations, with additional objectives including assessment of efficacy and further safety characterization. The company anticipates reporting initial data in mid-2026.

KTX-1001 is designed to selectively inhibit NSD2 and reduce levels of the epigenetic mark H3K36me2, restoring balance to gene expression and re-sensitizing tumor cells to therapy. In preclinical models, KTX-1001 reduced H3K36me2 levels in t(4;14) multiple myeloma, suppressed tumor growth and triggered cancer cell death in NSD2-high cell lines, and showed strong synergy when combined with proteasome inhibitors and immunomodulatory drugs. Early clinical data demonstrate clear evidence of target engagement through H3K36me2 suppression in patient samples and emerging signs of clinical activity in heavily pretreated patients, with a safety profile that supports ongoing evaluation of this novel epigenetic approach.

"Given the favorable safety profile we have already seen with KTX-1001, we are pleased to be able to participate in this next cohort evaluating KTX-1001 in combination with carfilzomib," said Edward Stadtmauer, MD, and principal investigator at Abramson Cancer Center at the University of Pennsylvania Perelman School of Medicine. "The emerging efficacy signals from this combination are encouraging. As an oral agent, KTX-1001 holds potential for use in earlier lines of therapy, both as a monotherapy and in combination with standard of care regimens."

About KTX-1001
KTX-1001 is a novel, first-in-class, potent, and selective methyltransferase inhibitor of the catalytic activity of MMSET/NSD2. It is an orally administered small molecule developed initially for the treatment of relapsed and refractory multiple myeloma, with a focus on patients with the t(4;14) translocation. This inhibitor offers a promising avenue for addressing this challenging high risk patient population.

About Multiple Myeloma
Multiple myeloma (MM) is the second most common hematologic malignancy, driven by the uncontrolled proliferation of plasma cells in the bone marrow. According to the American Cancer Society, approximately 36,000 new cases are diagnosed each year. While recent therapeutic advances have extended survival, MM remains incurable, and most patients eventually relapse. High-risk MM, defined by genetic abnormalities such as t(4;14) and other adverse prognostic markers, is associated with aggressive disease biology, shorter survival, and limited benefit from standard-of-care regimens. Addressing this high-risk population represents one of the greatest unmet needs in myeloma research and treatment.

About the KTX-1001 Phase 1 MMSET Clinical Trial
The Phase 1 clinical trial is a single-arm, open-label study in participants with relapsed and refractory multiple myeloma. It is a multi-part study with dose escalation followed by an expansion cohort in patients with the genetic translocation t(4;14) to evaluate the safety, tolerability, and preliminary efficacy of different doses of KTX-1001 in combination with standard of care and mezigdomide. For more information and participating centers, visit NCT05651932 and EUCTR: 2022-500801-41-00.

On September 16, 2025 Cytokinetics, Incorporated ("Cytokinetics") (Nasdaq: CYTK) reported the pricing of its offering of $650.0 million aggregate principal amount of 1.75% convertible senior notes due 2031 in a private placement (the "offering") to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Cytokinetics, SEP 16, 2025, View Source [SID1234656006]). The aggregate principal amount of the offering was increased from the previously announced offering size of $550.0 million.

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Key elements of the transaction include:

Primarily a refinancing transaction of the 3.50% convertible senior notes due 2027 (the "2027 notes"), which extends the maturity of the refinanced debt to 2031
Achieved a lower coupon of 1.75% and a higher conversion price of approximately $68.42 compared to the 2027 notes
Retiring approximately $399.5 million of the 2027 notes
Any remaining proceeds will be used to support the potential commercial launch of aficamten and for general corporate purposes, including potentially to retire the remaining 2027 notes before or at maturity of those notes that are not exchanged and refinanced pursuant to this transaction

The issuance and sale of the notes are scheduled to settle on September 19, 2025, subject to customary closing conditions. Cytokinetics also granted the initial purchasers of the notes an option to purchase, for settlement within a period of 13 days from, and including, the date the notes are first issued, up to an additional $100.0 million aggregate principal amount of notes.

The notes will be senior, unsecured obligations of Cytokinetics. The notes will accrue interest at an annual rate of 1.75%, payable semi-annually in arrears on April 1 and October 1 of each year, beginning on April 1, 2026. The notes will mature on October 1, 2031, unless earlier converted, redeemed or repurchased by Cytokinetics. Before July 1, 2031, noteholders will have the right to convert their notes only in certain circumstances. From and after July 1, 2031, noteholders may convert all or any portion of their notes at any time at their election until the close of business on the second scheduled trading day immediately before the maturity date. Cytokinetics will settle conversions by paying or delivering, as applicable, cash, shares of its common stock or a combination of cash and shares of its common stock, at Cytokinetics’ election. The initial conversion rate is 14.6156 shares of common stock per $1,000 principal amount of notes, which represents an initial conversion price of approximately $68.42 per share of common stock. The initial conversion price represents a premium of approximately 37.5% over the last reported sale price of $49.76 per share of Cytokinetics’ common stock on September 16, 2025. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events.

Cytokinetics’ may not redeem the notes at its election at any time before October 6, 2028. The notes will be redeemable, in whole or in part (subject to certain limitations), at Cytokinetics’ option at any time, and from time to time, on a redemption date on or after October 6, 2028 and, in the case of any partial redemption, on or before the 40th scheduled trading day immediately before the maturity date, at a cash redemption price equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date, but only if (i) the notes are "freely tradable" (as defined in the indenture for the notes) as of the date Cytokinetics sends the related redemption notice and all accrued and unpaid additional interest, if any, has been paid in full as of the first interest payment date occurring on or before the date such notice is sent and (ii) the last reported sale price per share of Cytokinetics’ common stock exceeds 130% of the conversion price for a specified period of time.

If a "fundamental change" (as defined in the indenture for the notes) occurs, then, subject to a limited exception, noteholders may require Cytokinetics to repurchase their notes at a cash repurchase price equal to the principal amount of the notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the fundamental change repurchase date.

Use of Proceeds: Cytokinetics estimates that the net proceeds from the offering will be approximately $632.0 million (or approximately $729.4 million if the initial purchasers fully exercise their option to purchase additional notes), after deducting the initial purchasers’ discounts and commissions and Cytokinetics’ estimated offering expenses. Cytokinetics intends to use:

approximately $402.5 million of the net proceeds from the offering to pay the cash portion of the consideration in the note exchange transactions as described below; and
the remainder of the net proceeds of this offering will be used (a) to support the potential commercial launch of aficamten, (b) to continue and expand the development program for aficamten, (c) to advance its development and research pipeline, and (d) for general corporate purposes, including potentially to retire the remaining 2027 notes before or at maturity of those notes that are not exchanged and refinanced pursuant to this transaction and working capital.

Cytokinetics expects to use approximately $402.5 million of the net proceeds from the offering and to issue 2,168,806 shares of its common stock in exchange for approximately $399.5 million aggregate principal amount of the 2027 notes in privately negotiated transactions (each, a "note exchange transaction") entered into concurrently with the pricing of the offering. The terms of each note exchange transaction will depend on a variety of factors, including the market price of Cytokinetics’ common stock and the trading price of the 2027 notes at the time of such note exchange transactions. No assurance can be given as to how much, if any, of the 2027 notes will be exchanged or the terms on which they will be exchanged. This press release is not an offer to exchange the 2027 notes, and the offering of the notes is not contingent upon the note exchange transactions.

In connection with any note exchange transaction, Cytokinetics expects that holders of the 2027 notes who agree to have their 2027 notes exchanged and who have hedged their equity price risk with respect to such 2027 notes (the "hedged holders") will, concurrently with, or shortly after, the pricing of the notes, unwind all or part of their hedge positions by buying Cytokinetics’ common stock and/or entering into or unwinding various derivative transactions with respect to its common stock. The amount of Cytokinetics’ common stock to be purchased by the hedged holders or the notional number of shares of Cytokinetics’ common stock underlying such derivative transactions may be substantial in relation to the historic average daily trading volume of Cytokinetics’ common stock. This activity by the hedged holders could increase (or reduce the size of any decrease in) the market price of Cytokinetics’ common stock, including concurrently with the pricing of the notes, resulting in a higher effective conversion price for the notes. Cytokinetics cannot predict the magnitude of such market activity or the overall effect it will have on the price of the notes or its common stock.

The offer and sale of the notes, any shares of common stock issuable upon conversion of the notes and any shares of common stock issuable in connection with any note exchange transaction have not been, and will not be, registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification thereof under the securities laws of any state or jurisdiction.

On September 16, 2025 Biogen Inc. (Nasdaq: BIIB) reported that Priya Singhal, Head of Development, will participate in a fireside chat during the Bernstein 2nd Annual Healthcare Forum (Press release, Biogen, SEP 16, 2025, View Source [SID1234656005]). The webcast will be live on Wednesday, Sept 24, 2025, at 11:20 a.m. ET. To access the live webcast, please visit the Investors section of Biogen’s website at investors.biogen.com. An archived version of the webcast will be available for at least 30 days following the presentation.

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On September 16, 2025 Lantern Pharma Inc. (NASDAQ: LTRN), a leading artificial intelligence (AI)-driven oncology company leveraging its proprietary RADR platform to accelerate targeted cancer therapies, reported the successful completion of its Phase 1a clinical trial (NCT05933265) for LP-184 (Press release, Lantern Pharma, SEP 16, 2025, View Source [SID1234656004]). The trial met all primary endpoints, demonstrating a favorable safety and pharmacokinetic (PK) profile, and early signs of antitumor activity. Enrollment is complete, with several patients continuing treatment due to ongoing clinical benefit.

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The open-label, multicenter, non-randomized study evaluated LP-184 in 63 patients with advanced relapsed or refractory solid tumors, including GBM. Primary objectives focused on safety, tolerability, PK, and determining a recommended Phase 2 dose (RP2D) when administered on Days 1 and 8 of a 21-day cycle.

Summary of Preliminary Phase 1a Safety and Pharmacokinetic Observations

LP-184 exhibited a robust safety profile, with no dose-limiting toxicities in the majority of cohorts and low incidence of discontinuations, interruptions, or delays due to drug-related adverse events. Adverse events were predominantly Grade 1 or 2, including manageable nausea and vomiting—consistent with alkylating agents—that resolved without significant intervention. The low rate of Grade 3+ events (minimal across the study) underscores LP-184’s tolerability, making it well-suited for potential monotherapy or combinations with agents like PARP inhibitors and immunotherapies, where preclinical synergies have been observed.

PK data confirmed that therapeutic concentrations were achieved at dose levels 8 (0.25 mg/kg) and above, aligning with preclinical models and supporting dose optimization for future trials. These observations will help further de-risk LP-184, enabling efficient advancement in biomarker-enriched populations identified via our RADR AI platform.

Summary of Preliminary Phase 1a Antitumor Observations

Promising antitumor activity emerged, particularly at dose levels 8 (0.25 mg/kg) and above, where therapeutic exposures were attained. Disease control was achieved in 48% (10/21) of evaluable patients after two cycles, including in heavily pre-treated cases. The median number of prior lines of therapy was 3; some patients had up to 8 prior lines of therapy.

Notable highlights from the overall study include:

Clinical benefit observed in 4 of 16 recurrent GBM patients previously exposed to temozolomide, lomustine, and/or radiation.
Marked reductions in target cancer lesions among patients with CHK2, ATM, BRCA1 and STK11/KEAP1 mutations, spanning colon cancer, thymic carcinoma, gastrointestinal stromal tumor (GIST), and NSCLC.
A NSCLC patient with DNA damage response (DDR) mutations, refractory to immunotherapy, achieved nearly two years of clinical benefit and remained on treatment.
Two patients at dose level 10 (0.39 mg/kg) maintain disease control beyond six months and continue on therapy.
These signals in DDR-deficient tumors further support LP-184’s synthetic lethal mechanism and highlight its potential in precision oncology.

"On behalf of our dedicated team, we extend our sincere gratitude to the patients, families, investigators, and clinical staff whose commitment drove the success of our Phase 1a LP-184 trial, establishing a robust safety profile with encouraging signals of activity at therapeutic doses," said Panna Sharma, Chief Executive Officer of Lantern Pharma. "Leveraging our RADR AI platform, we’re now positioning LP-184 for targeted Phase 1b and Phase 2 studies. Our goals are to position LP-184 to address critical unmet needs in TNBC, NSCLC, and other DDR-deficient cancers, which can unlock significant value for patients and investors alike."

Recommended Phase 2 Dose and LP-184 Future Development Plan

The Safety Review Committee supported an RP2D of 0.39 mg/kg in this regimen, with provisions for intra-patient escalation, based on the trial’s evaluation of safety, tolerability, and PK data. Building on these results, Lantern is developing plans to advance multiple Phase 1b/2 trials, prioritizing the following disease indications:

TNBC in combination with Olaparib (a PARP inhibitor), with potential for ctDNA as an early response biomarker to support accelerated approval pathways.
NSCLC with STK11/KEAP1 co-mutations, with or without immunotherapy.
Bladder cancer in a trial to be conducted as an investigator-led study in Denmark with patients harboring DNA damage repair genetic alterations.
These initiatives target high-value indications with substantial market potential and high clinical need.

Data Cutoff Date and Future Publications and Presentations

The data cutoff for the observations described in this release is August 26, 2025. Comprehensive results from the LP-184 Phase 1a trial are being prepared for peer-reviewed publications and presentations at upcoming oncology conferences.