Pyxis Oncology, a clinical-stage company focused on developing next-generation therapeutics to target difficult-to-treat cancers, and Apexigen, a clinical-stage biopharmaceutical company focused on discovering and developing innovative antibody therapeutics for oncology, confirmed that the companies have signed a definitive agreement by which Pyxis Oncology will acquire Apexigen in an all-stock transaction for an implied value of $0.64 per Apexigen share.

For each share of Apexigen, Pyxis Oncology will issue 0.1725 shares of its common stock, par value $0.001 per share, for a total enterprise value of approximately $16 million.

“This acquisition uniquely positions Pyxis Oncology at the forefront of antibody-drug conjugate (ADC) innovation by adding humanized antibody generation to our Flexible Antibody Conjugation Technology (FACT) ADC toolkit acquired from Pfizer, and expands our clinical pipeline into Phase 2 in select solid tumor types by leveraging our founding heritage of immuno-oncology expertise—all while maintaining our cash runway into 2025,” said Lara S. Sullivan, M.D., President and Chief Executive Officer of Pyxis Oncology.

FACT technology Platform
The Flexible Antibody Conjugation Technology (FACT) technology platform, licensed from Pfizer, in 2021, is designed to facilitate creation of next-generation ADCs like PYX-201 that have the potential for improved anti-tumor activity, safety and tolerability. [1]

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Compared to traditional ADC approaches, the FACT platform is based upon technical improvements to allow site-specific payload conjugation, linker stability and payload potency.[1]

In preclinical studies, the FACT platform technology has demonstrated a superior therapeutic index over currently marketed auristatin based ADCs. FACT site-specific conjugation of vc-0101 to engineered cysteine residues exhibits improved therapeutic Index over ado-trastuzumam emtansine (Kadcyla®; Genentech/Roche) and conjugation technology used in brentuximab vedotin (Adcetris®; Seagen) and enfortumab vedotin (Padcev®; Astellas Pharma/Seagen).[1]

Sotigalimab
As part of the acquisition, Pyxis oncology will add Sotigalimab (APX005M), a differentiated, potentially best-in-class anti-CD40 antibody in clinical development for liposarcoma, melanoma, and other cancers, to its development pipeline.  The investigational agent uniquely binds to CD40 and has been engineered to be effector function silent which has the potential to overcome dosing limitations of other anti-CD40 approaches.

Sotigalimab is currently being evaluated in an investigator-initiated Phase 2 trial in combination with doxorubicin dedifferentiated liposarcoma (DDLPS), a rare subtype of liposarcoma as well as a Phase 2 trial in combination with nivolumab in patients with PD-(L)1 blockade refractory melanoma.

“Sotigalimab is a CD40 agonist with best-in-class potential. It has demonstrated clear anti-cancer activity in patients who previously progressed on PD-(L)1 inhibitors, with impressive, durable remissions,” Sullivan said.

“[However,] this activity may not only be synergistic with immune checkpoint inhibitors, but also rescue their activity in patients who are refractory or have relapsed. We are excited about the potential to acquire the commercially and clinically validated APXiMAB platform to generate novel antibodies that can be optimized for targeted payload delivery. In combination with our proprietary FACT platform, we believe Pyxis Oncology is positioned with an unmatched, end-to-end system for designing and producing novel, next-generation ADC candidates with improved potency, stability and tolerability,” Sullivan explained.

Ongoing evaluation
Sotigalimab has been evaluated in more than 500 patients in clinical trials and demonstrated strong activity, including rapid, deep and durable responses and a favorable tolerability profile, across multiple difficult-to-treat tumor types. Key results presented from two Phase 2 studies include:

  • Sotigalimab plus nivolumab (Opdivo®; Bristol-Myers Squibb) demonstrated durable activity and prolonged responses in patients with anti-PD-(L)1 refractory melanoma.
    • 15.2% of patients achieved partial responses (PR), with durations of 4.2 to 24.7 months
    • 30.3% of patients achieved stable disease (SD) lasting up to 14+ months
  • Sotigalimab plus doxorubicin demonstrated robust and prolonged responses and encouraging tolerability in patients with advanced soft tissue sarcoma (STS). Updated data are anticipated to be presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting in early June.
    • Prolonged durations of PR and SD achieved across all STS patients and the DDLPS subtype of up to 25+ months
    • 60% of patients achieved SD, with durations of 1.3 to 11 months
    • 20% of patients achieved PRs, with durations of 1.4 to 23.4 months
      • A sub-analysis found patients with DDLPS achieved a median progression free survival (mPFS) of 12.45 months, more than double historical responses expected following chemotherapy alone

Across all studies reported to date, sotigalimab has been well tolerated. In the first-in-human monotherapy dose-escalation study, the most common related grade ≥3 TEAEs experienced by 2 or more subjects (N,%) were cytokine release syndrome (4, 9.3%), AST increase (2, 4.7%), fatigue (2, 4.7%), hypotension (2, 4.7%), syncope (2, 4.7%), and thrombocytopenia (2, 4.7%).

The safety profile in combination with nivolumab in patients with melanoma was in line with expectations for each drug independently. Reported grade ≥3 related TEAEs consisted of transient increases of alanine aminotransferase (2 patients) and increase of aspartate aminotransferase (2 patients). In this and other previously reported studies in which sotigalimab was administered in combination with an anti-PD-1 or chemotherapy in patients with melanoma or esophageal/GEJ cancers, no additive or synergistic toxicities were observed.

Proprietary antibody discovery platform
The companies will also continue using APXiMAB, Apexigen’s proprietary antibody discovery platform, wjich is designed to leverages rabbit monoclonal antibody and Mutation Lineage Guided humanization technologies.

Apexigen’s discovery platform has enabled the discovery of multiple protein therapeutic product candidates against a variety of molecular targets, including targets that are difficult to drug with conventional antibody technologies. APXiMAB is designed to create antibodies with high affinity, high specificity and high stability. Fo-date, our antibodies discovered through the use of this platform are currently in clinical development by Apexigen’s licensees, and a fifth received FDA approval in 2019 and is marketed as brolucizumab-dbll (Beovu®; Novartis) in over 70 countries.

Upon closing, Pyxis Oncology will be eligible for royalty income generated from partnered programs developed using APXiMAB.

Foundational work
“I am proud of the foundational work Apexigen has done to advance sotigalimab into Phase 2 trials across multiple solid tumor types,” said Xiaodong Yang, M.D., Ph.D., Chief Executive Officer of Apexigen.

“Apexigen and Pyxis Oncology share a common vision of bringing innovative solutions to oncology patients. With Pyxis Oncology’s strong cash position and its commitment to further sotigalimab’s development, we believe that this transaction will greatly enhance the opportunity to efficiently advance sotigalimab for patients suffering from a variety of difficult-to-treat cancers. Additionally, coupling our APXiMAB antibody platform with Pyxis Oncology’s complementary ADC technology platform will magnify the therapeutic potential of the APXiMAB platform.,” Yang added.

Post-Closing Operations and Leadership
Effective as of the closing of the transaction, the combined company will trade on Nasdaq under the ticker symbol “PYXS” and the existing Pyxis Oncology leadership team will continue to be responsible for all executive positions, including Lara S. Sullivan, M.D., as President and Chief Executive Officer, Pamela Connealy, as Chief Financial Officer and Chief Operating Officer, and Jan Pinkas, Ph.D., as Chief Scientific Officer.

Effective June 15, 2023, Jay M. Feingold, M.D., Ph.D., will step down as Chief Medical Officer to pursue other opportunities. Dr. Feingold will remain an advisor to Pyxis Oncology until a successor is named.

“I would like to thank Jay for his valuable contributions to the Company over the past two years. During Jay’s tenure, Pyxis Oncology transitioned from a preclinically focused organization to a clinical-stage company with two ongoing Phase 1 trials. I look forward to working closely with Xiaodong to continue the important work we are doing to advance new therapeutic options for patients,” Sullivan said.

The definitive merger agreement has been approved by the Boards of Directors of each company and is anticipated to close by mid-2023, subject to the satisfaction or waiver of customary closing conditions, including approval by the stockholders of Apexigen and the effectiveness of a registration statement on Form S-4 to register the shares of Pyxis Oncology common stock to be issued in connection with the transaction.

Clinical trials
Study of PYX-201 in Solid Tumors – NCT05720117

Highlights of prescribing Information
Nivolumab (Opdivo®; Bristol-Myers Squibb) [Prescribing Information]
Ado-trastuzumam emtansine (Kadcyla®; Genentech/Roche) [Prescribing Information]
Brentuximab vedotin (Adcetris®; Seagen)[Prescribing Information]
Enfortumab vedotin (Padcev®; Astellas Pharma/Seagen)[Prescribing Information]

Reference
[1] First Patient Dosed in Phase 1 Trial with Pyxis Oncology’s PYX-201. ADC Review | J. Antibody-drug Conjugates, March 18, 2023. Online. Last accesses on May 24, 2023,

Featured image by Adeolu Eletu on Unsplash. Used with permission.

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