"Dear Fellow Shareholders,

Over the past several months, our Board of Directors and management team conducted a comprehensive review of our development portfolio, capital allocation priorities and long-term strategy. Following this review, we believe the best path to creating long-term shareholder value is to prioritize the advancement of PDS0301, our tumor-targeted immunocytokine, while pursuing strategic partnership opportunities for PDS0101.

The oncology treatment landscape is rapidly evolving with the emergence of various precision medicines. Despite these advances, treatment resistance and limited durability of response remain significant challenges for many patients with advanced solid tumors. Based on supportive preclinical and clinical data, we believe PDS0301 has the potential to address these challenges by precisely targeting and remodeling the tumor microenvironment, potentially enhancing the effectiveness and durability of current and emerging oncology therapies. To address this medical need, we have designed PDS0301 for use, in combination with other oncology therapies, to remodel the tumor microenvironment to potentially promote more effective anti-tumor responses in patients. We believe the remodeling of the tumor microenvironment is an important factor in addressing treatment resistance and reversing disease progression. Further, this mechanism could enable PDS0301 to complement a broad range of current and emerging oncology therapies, including RAS pathway inhibitors, bispecific antibodies, ADCs and radioligand therapies.

We concluded that our resources should be redirected toward PDS0301, where we believe the combination of encouraging clinical data, development opportunity and capital requirements provide a potentially more attractive path to long-term shareholder value.

Phase 2 mCRC Results

Patients with metastatic microsatellite stable (MSS) and mismatch repair-proficient (pMMR) colorectal cancer, particularly those with liver metastases, continue to face substantial unmet medical needs, and median overall survival is reported to be less than 10 months and objective response rates (ORR) less than 25%1. Clinical data generated in collaboration with the National Cancer Institute demonstrated encouraging and durable activity, including a 71% ORR at 6 months and an 80% 24-month survival rate in patients with metastatic MSS and pMMR colorectal cancer and liver metastases2. Together with safety observed in more than 380 treated patients, these findings strengthen our conviction that PDS0301 has the potential to address one of the more significant limitations of current oncology therapies.

Strategic Partnering Opportunities for PDS0101

We have decided that we will cease further internal investment in the PDS0101 Phase 3 VERSATILE-003 trial, including the discontinuation of the VERSATILE-003 Phase 3 trial, and intend to pursue strategic partnerships or other externally funded opportunities for the continued development of PDS0101. This decision follows a comprehensive assessment of the capital, time and resources required to complete the Phase 3 trial and support commercialization of PDS0101. This decision reflects our commitment to disciplined capital allocation rather than a change in our view of the underlying PDS0101 science and clinical data. We believe the strength of the Phase 2 clinical results allows us to preserve the potential value of PDS0101 through a strategic partnership.

Why We Believe PDS0301 Represents Our Greatest Opportunity

Our objective is to establish PDS0301 as a foundational component of next-generation oncology therapies for multiple difficult-to-treat solid tumors.

We believe PDS0301 offers several important differentiators:

  • Encouraging efficacy as a single agent (monotherapy) in advanced, recurrent cancer.
  • Encouraging efficacy with chemotherapy in difficult-to-treat metastatic colorectal cancer.
  • More than 380 patients treated with an encouraging safety and tolerability profile.
  • A mechanism designed to remodel the tumor microenvironment and to reshape the anti-tumor immune response in patients, leading to more effective and more durable or long-lasting therapy. The mechanism also has the potential to improve the durability of ADCs, bispecific antibodies, radioligands, targeted therapies and immunotherapies.
  • Clinical activity and tolerability observed across multiple difficult-to-treat solid tumors as a single agent and in double and triple combinations.
  • A Phase 2b development strategy designed to take into account feedback from the FDA.

Although metastatic colorectal cancer is our lead development program, our maturing clinical data in various solid tumors suggests that PDS0301 may have broader application. By targeting the tumor microenvironment rather than a single oncogenic pathway, PDS0301 appears to have applicability across multiple difficult-to-treat solid tumors which could result in several combination oncology therapy strategies.

Beyond colorectal cancer, PDS0301 is also being evaluated in recurrent prostate cancer, metastatic castration resistant prostate cancer, Kaposi sarcoma, HPV16-positive cancers, and other National Cancer Institute-sponsored clinical trials, providing additional opportunities to demonstrate the breadth of PDS0301.

Looking Ahead

A randomized Phase 2b trial with PDS0301 has been designed taking into account feedback received from the FDA and is intended to generate meaningful clinical data with disciplined capital investment.

Over the next 18 to 24 months, we expect to:

  • Advance PDS0301 through a randomized Phase 2b development program.
  • Identify and assess strategic partnering opportunities for PDS0101.
  • Maintain disciplined capital allocation while delivering meaningful clinical and business milestones.

     

We believe PDS Biotechnology is well positioned at the intersection of one of oncology's most important emerging trends: improving the effectiveness and durability of oncology therapies through precision remodeling of the tumor microenvironment. By focusing our resources on PDS0301, identifying strategic partnerships for PDS0101, and executing with financial discipline, we believe we can create meaningful long-term value for both patients and shareholders. We look forward to updating you on our progress as we move forward with this new strategy."

Sincerely,

Frank Bedu-Addo, Ph.D.

Chief Executive Officer, Director