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Pyxis Oncology Announces Portfolio Prioritization, Focusing Resources on its Lead Clinical Program, PYX-201

On December 19, 2024 Pyxis Oncology, Inc. (Nasdaq: PYXS), a clinical-stage company developing next-generation therapeutics for difficult-to-treat cancers, reported a portfolio prioritization, focusing resources on advancing its lead clinical program, PYX-201, a first-in-concept antibody-drug conjugate (ADC) with a microtubule inhibitor (optimized auristatin) payload that uniquely targets Extradomain-B Fibronectin (EDB+FN), a non-cellular structural component within the tumor extracellular matrix (Press release, Pyxis Oncology, DEC 19, 2024, View Source [SID1234649222]).

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In November 2024, Pyxis Oncology reported positive preliminary data from the ongoing Phase 1 dose-escalation study of PYX-201, evaluating its safety and efficacy in multiple solid tumor types. Among patients with HNSCC, PYX-201 achieved a confirmed 50% objective response rate (ORR) based on RECIST 1.1 criteria, including one complete response and a disease control rate (DCR) of 100% in six heavily pretreated HPV-positive and HPV-negative evaluable patients with a median of four prior lines of therapy.

Across six solid tumor types of interest at therapeutically active dose levels, including HNSCC, ovarian, non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple-negative breast cancer (TNBC), and sarcoma, PYX-201 (n=31) achieved a 26% ORR in the Phase 1 trial, with dose-dependent responses observed including patients who had previously progressed on taxanes. The data supports further development in both monotherapy and combination therapy expansion trials, including a frontline HNSCC study in combination with pembrolizumab, with patient dosing in both the monotherapy and combination therapy trials expected to begin in early 2025.

The portfolio prioritization further supports a robust development plan for PYX-201 in several dose expansion studies, including monotherapy in 2/3L HNSCC, in combination with pembrolizumab in 1/2L+ HNSCC, as well as pembrolizumab combination studies in other solid tumors including HR+/HER2- and triple-negative breast cancer. Preliminary data from these cohorts is expected across both the second half of 2025 and the first half of 2026.

Details on the PYX-201 Phase 1 dose-escalation trial and preliminary data presented in November are available on the Events & Presentations page in the Investor Relations section of Pyxis Oncology’s website at ir.pyxisoncology.com.

Pipeline Prioritization

Pyxis Oncology’s second clinical program, PYX-106 — a fully human IgG1 monoclonal antibody targeting Siglec-15 — is being deprioritized to allocate resources toward advancing the lead asset, PYX-201. As a result, Pyxis Oncology has decided to suspend further clinical investment in PYX-106, which was in-licensed from Biosion Inc., with Biosion retaining rights for Greater China.

To date, the Phase 1 monotherapy trial of PYX-106 enrolled 45 patients with advanced solid tumors. PYX-106 was observed as generally safe and well-tolerated across all tested doses, ranging from 0.5 mg/kg to 22.5 mg/kg. At this time, a maximum tolerated dose has not been established. The pharmacokinetic and pharmacodynamic results demonstrated dose-proportional pharmacokinetics, a half-life of 9 to 11 days, no detection of antidrug antibodies in a variety of heavily pretreated solid tumors across tested dose levels.

"Deprioritizing the PYX-106 clinical program as a monoclonal antibody represents a strategic and judicious use of our resources, allowing us to focus on advancing PYX-201," said Lara S. Sullivan, M.D., President and Chief Executive Officer of Pyxis Oncology. "We are excited about the potential of PYX-201, an innovative, first-in-concept ADC uniquely designed to target the tumor extracellular matrix. The positive preliminary PYX-201 Phase 1 data we presented last month reinforces our confidence in the promise of this program, particularly in addressing unmet needs in HNSCC in both monotherapy and combination therapy settings."

Unleashing the potential of Immuno-oncology therapies

On December 19, 2024 Xilio therapeutics presented its corporate presentation (Presentation, Xilio Therapeutics, DEC 19, 2024, View Source [SID1234649221]).

Phio Pharmaceuticals Announces Positive Safety Monitoring Committee (SMC) Recommendation to continue to Third Dose Cohort in its Clinical Study of PH-762

On December 19, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical-stage biotechnology company that develops therapeutics using its INTASYL siRNA gene silencing technology to make the body’s immune cells more effective in killing cancer cells. Phio reported that the Safety Monitoring Committee (SMC) recommended dose escalation in its Phase 1b clinical trial designed to evaluate the safety and tolerability of PH-762 in the treatment of Stages 1, 2, and 4 cutaneous squamous cell carcinoma, Stage 4 melanoma and Stage 4 Merkel cell carcinoma (Press release, Phio Pharmaceuticals, DEC 19, 2024, View Source [SID1234649220]).

In this Phase 1b clinical study with PH-762, dosed intratumorally, the second cohort had enrolled 4 patients who were diagnosed with cutaneous squamous cell carcinoma. At Day 36 (tumor excision), the first two patients who completed treatment showed a complete response (100% tumor clearance and a partial response 90% clearance), respectively. Pathology data assessing efficacy data on the remaining 2 patients is forthcoming.

The intratumoral injections have been well tolerated. There have been no dose-limiting toxicities, or serious adverse events in participants receiving intratumoral PH-762.

"Safety and efficacy data from our clinical trial continues to be encouraging as we develop PH-762 for the treatment of cutaneous carcinomas" said Mary Spellman MD, Phio’s acting Chief Medical Officer. "We look forward to continued enrollment in the clinical study."

PharmaMar completes enrollment for phase III LAGOON study with Zepzelca® (lurbinectedin) for the treatment of small cell lung cancer

On December 19, 2024 PharmaMar (MSE: PHM) reported that the Phase III LAGOON clinical trial, which evaluates Zepzelca (lurbinectedin) for the treatment of patients with relapsed small cell lung cancer (SCLC), has achieved its recruitment target of 705 patients (Press release, PharmaMar, DEC 19, 2024, View Source [SID1234649219]).

LAGOON is a randomized (1:1:1), multicenter, open-label Phase III clinical trial with three arms: in the first arm, patients receive lurbinectedin as monotherapy; in the second arm, lurbinectedin is administered in combination with irinotecan; and in the third arm, patients are treated with physician’s choice of topotecan or irinotecan. The study enrolled patients with SCLC whose disease has progressed after one prior line of platinum-based chemotherapy, with or without anti-PD-1 or anti-PD-L1 agents.

The primary objective of the trial is to evaluate overall survival (OS) and progression-free survival (PFS) is one of the secondary endpoints. Top-line results from the study are anticipated in the first quarter of 2026.

Lurbinectedin received accelerated approval from the FDA in June 2020 for the treatment of adult patients with metastatic SCLC whose disease has progressed during or after platinum-based chemotherapy. Since then, it has been approved in 17 territories, including recently in China, although in Europe it has only received approval in Switzerland.

Lurbinectedin is also being investigated in the Phase 3 IMforte clinical trial in combination with atezolizumab compared to atezolizumab alone when administered as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) following induction therapy with carboplatin, etoposide and atezolizumab. As previously announced in October 2024 by Jazz Pharmaceuticals and PharmaMar, the preliminary results from the IMforte trial demonstrated a statistically significant improvement in the primary endpoints of OS and PFS, as assessed by an independent review facility (IRF), for the combination compared to treatment with atezolizumab alone.

SCLC accounts for 15% of all lung cancer diagnoses and is among the most aggressive cancer types. It is characterized by its rapid growth, invasive nature, and early metastasis. Approximately 70% of cases are diagnosed at advanced stages. While the disease often initially responds well to treatment, it tends to recur frequently.

Entry into a Material Definitive Agreement

On December 19, 2024, Personalis, Inc. (the "Company") reported to have entered into an investment agreement (the "Investment Agreement") with Merck Sharp & Dohme LLC ("Merck") pursuant to which Merck has agreed to purchase from the Company 14,044,943 shares (the "Shares") of the Company’s common stock, par value $0.0001 per share (the "Common Stock"), at a price per share of $3.56, representing the last reported closing price of the Common Stock on The Nasdaq Global Market on December 18, 2024, for gross proceeds to the Company of approximately $50.0 million (Filing, 8-K, Personalis, DEC 19, 2024, View Source [SID1234649218]). The closing is expected to occur on or about December 19, 2024 (the "Closing Date"). Pursuant to the terms of the Investment Agreement, the Company agreed to reserve $10.0 million of the proceeds to open an ISO-certified laboratory in a region outside of the United States, with such region mutually agreed upon by the Company and Merck.

Pursuant to the terms of the Investment Agreement, Merck agreed to certain customary standstill restrictions that apply from the Closing Date until the earlier of (a) the second anniversary of the Closing Date and (b) the first time that Merck and its affiliates no longer own at least 50% of the Company’s shares owned by Merck immediately following the Closing Date (this clause (b), the "Investor Rights Period," and the earlier of clause (a) and (b), the "Standstill Period"). These standstill restrictions will lapse prior to the end of the Standstill Period if the Company publicly announces the entry into a definitive agreement providing for a change of control transaction. In addition, during the Investor Rights Period, the Company has agreed to provide Merck with certain information and strategic transaction notification rights, including to notify Merck in certain circumstances and subject to certain specified exceptions if (a) the Company receives a bona fide offer, indication of interest or proposal from a third party for a change of control transaction (a "Proposal") or (b) the Company’s board of directors commences a process for solicitation of offers or indications of interest for a change of control transaction (a "Sale Process"). Subject to specific exceptions, the Company agreed to provide Merck with a reasonable opportunity to respond to a Proposal or participate in a Sale Process in a similar manner to other participants. In addition, during the Investor Rights Period the Company agreed to provide Merck with the opportunity to participate pro rata in future equity or equity-linked offerings of the Company, subject to specified exceptions.

Merck also agreed to certain voting commitments under the Investment Agreement that, during the Standstill Period, require Merck to vote, subject to specified exceptions, any shares of Common Stock that Merck owns in accordance with the recommendations of the Company’s board of directors. Such voting commitments generally apply to director nominations for any meeting of the Company’s stockholders, amendments to the Company’s charter to increase the authorized shares of Common Stock, various compensation-related matters, and ratification of the Company’s auditors. Merck also agreed not to transfer (a) any Shares to any third party, subject to certain specified exceptions, for 90 days following the Closing Date or (b) at any time any Shares or other securities acquired under the Investment Agreement to certain restricted parties and activist investors specified in the Investment Agreement.

Pursuant to the terms of the Investment Agreement, the Company agreed to file a registration statement with the U.S. Securities and Exchange Commission within 30 calendar days of the date of sale of the Shares to register the Shares for resale.

The Investment Agreement contains customary representations, warranties and covenants that were made solely for the benefit of the parties to the Investment Agreement. Such representations, warranties and covenants (a) are intended as a way of allocating risk between the parties to the Investment Agreement and not as statements of fact, and (b) may apply standards of materiality in a way that is different from what may be viewed as material by stockholders of, or other investors in, the Company. Accordingly, the Investment Agreement is included with this filing only to provide investors with information regarding the terms of the transaction and not to provide investors with any other factual information regarding the Company. Investors should not rely on the representations, warranties and covenants or any descriptions thereof as characterizations of the actual state of facts or condition of the Company or any of its subsidiaries or affiliates. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Investment Agreement, which subsequent information may or may not be fully reflected in public disclosures.

The foregoing summary of the Investment Agreement is qualified in its entirety by reference to the full text of the Investment Agreement, a copy of which is attached to this report as Exhibit 4.1, which is incorporated herein by reference.