Contradictions Emerge in Clinical Trial Strategy: Shifting Study Populations, Dosing Adjustments, and GLP-1 Agonist Choices

Guidance:

• Phase IIb PLATEAU to begin in Q1 2026; interim DEXA analysis at 36 weeks anticipated in Q1 2027.
• FDA provided two acceptable regulatory pathways: ≥5% placebo‑corrected incremental weight loss at 52 weeks OR clinically meaningful preservation/improvement in physical function/body composition.
• Cash position: $15.8M (Sep 30, 2025) plus ~$23.4M net proceeds (Oct 31, 2025); company states cash is sufficient to fund operations through the PLATEAU interim analysis but additional capital will be required thereafter.

Business Commentary:

* Regulatory Clarity and Clinical Development: - Veru obtained regulatory clarity from the FDA regarding the development of enobosarm in combination with GLP-1 receptor agonists, with at least two possible regulatory pathways forward based on incremental weight loss. - This regulatory guidance cleared the way for Veru's Phase IIb PLATEAU clinical trial, which aims to assess enobosarm's effect on weight loss and physical function in a specific patient population.

• Financial Position and Funding:
• Veru's cash and cash equivalents and restricted cash balance was $15.8 million as of September 30, 2025, with subsequent net proceeds from a public offering totaling approximately $23.4 million, enhancing financial stability.

• These funds are to support the ongoing Phase IIb PLATEAU clinical study, which is expected to begin in the first quarter of 2026.

• Pipeline and Product Developments:

• Veru's obesity program showed promising results in a Phase IIb QUALITY clinical trial, demonstrating that enobosarm preserved lean mass and enhanced fat loss when combined with semaglutide.

• The successful results aligned with the FDA's guidance, emphasizing the clinical significance of preserving muscle mass and physical function in older patients with obesity.

• Strategic Shifts and Market Targeting:

• Veru sold its FC2 Female Condom business for $18 million in cash, allowing the company to focus exclusively on drug development, particularly in the cardiometabolic and inflammatory diseases space.
• The shift emphasizes the company's strategic focus on expanding its drug pipeline and targeting areas with substantial market potential, such as the obesity market, which includes a significant segment covered by Medicare reimbursement.

Sentiment Analysis:

Overall Tone: Positive

• Management highlighted positive Phase IIb QUALITY results (3 mg enobosarm + semaglutide: 100% lean mass preservation, 12% greater fat loss at 16 weeks), 'positive safety profile', constructive FDA guidance with two regulatory pathways, and successful financing (~$23.4M net proceeds) enabling the upcoming PLATEAU trial.

Q&A:

• Question from William Wood (B. Riley Securities, Inc., Research Division): Will PLATEAU allow any GLP‑1 (semaglutide/tirzepatide/oral forms) or will it be limited to a single agent; and how should we view the 5% weight‑loss bar across different background GLP‑1 agents?
  Response: They will use a single GLP‑1 to avoid variability; tirzepatide is the placeholder but semaglutide could be chosen — study will be tied to that single agent when assessing the incremental weight‑loss bar.

• Question from William Wood (B. Riley Securities, Inc., Research Division): If incremental weight loss <5% occurs, can a functional endpoint (e.g., stair climb) be primary in Phase III, or must it be an and/or dual endpoint?
  Response: The Phase IIb is designed as a 'mini Phase‑III' to determine the path: if incremental weight loss meets FDA criteria you proceed with that (and include function in label); if not, clinically meaningful physical‑function/body‑composition endpoints can serve as the primary endpoint in Phase III.

• Question from William Wood (B. Riley Securities, Inc., Research Division): Why is PLATEAU targeting ≥65 years (vs prior ≥60) — FDA guidance, reimbursement, or the most in‑need population?
  Response: They target ≥65 because this subgroup is most informative for demonstrating functional benefit (higher sarcopenic risk); if incremental weight loss is achieved in ≥65, it should generalize to younger patients, and Phase III can prespecify older subsets.

• Question from Rohan Mathur (Oppenheimer & Co. Inc., Research Division): Will there be regulatory flexibility around demonstrating weight‑loss versus muscle/function outcomes in PLATEAU?
  Response: Yes — the 5% placebo‑corrected threshold is the clear stake in the ground, but FDA accepts clinically meaningful physical‑function and mobility measures (stair climb, mobility disability assessments, PROs) as alternative/complimentary evidence to support approval.

Contradiction Point 1

Study Population and Focus

It involves a shift in the target population and study focus, which could impact the overall strategy and outcomes of clinical trials.

Which population is PLATEAU targeting now, and why? - William Wood (B. Riley Securities)

2025Q4: The Phase IIb QUALITY study showed physical limitations and physical function decline in older patients, leading us to focus on patients over 65. This is to ensure we have the right patient population for physical function endpoints. - Mitchell Steiner(CEO, President)

Regarding the obesity study with SQLZ, can you explain the rationale for focusing on patients over 60? - Dennis Ding (Jefferies)

2023Q2: The QUALITY trial, we are looking at patients that are 60 and older, and we are using a composite endpoint. - Mitchell Steiner(CEO, President)

Contradiction Point 2

Enobosarm Dosing and Combination Therapy

It involves changes in the Enobosarm dosing strategy and combination therapy, which could affect the efficacy and safety of the treatment.

Given the PLATEAU study outcomes, will there be regulatory flexibility regarding weight loss and muscle function? - Rohan Mathur (Oppenheimer & Co.)

2025Q4: The Enobosarm monotherapy arms and combination arms with Abemaciclib are expected to perform significantly better than the active control due to positive early results from the Stage 1 run-in portion. - Mitchell Steiner(CEO, President)

What range of overall response rates in the Enabler study's Stage 1 do you expect could support accelerated approval? - Yi Chen (H.C. Wainwright)

2023Q2: We expect, in the various arms, a 28-day treatment with Enobosarm in the dose level that is now known to be effective to some clinically meaningful degree in healthy older adults, to improve the physical function. - Mitchell Steiner(CEO, President)

Contradiction Point 3

Patient Population and Study Design in Phase IIb Trial

It involves the selection criteria and focus of the Phase IIb trial, which is crucial for the success of the study and the potential patient population for future treatments.

Which population is PLATEAU targeting currently, and why? - William Wood (B. Riley Securities)

2025Q4: The Phase IIb QUALITY study showed physical limitations and physical function decline in older patients, leading us to focus on patients over 65. This is to ensure we have the right patient population for physical function endpoints. We're targeting patients most in need, who are at risk for sarcopenia, and potentially Medicare beneficiaries. - Mitchell Steiner(CEO)

What are your expectations for the FDA Phase II meeting outcome, and could there be pushback on functional endpoints or patient population? How will you communicate the results? - Gary Jay Nachman (Raymond James & Associates, Inc.)

2025Q3: However, we can certainly broaden the population if the FDA is comfortable with that and provide a more definitive answer as to whether this treatment will be helpful across the variety of healthy populations or whether it will be focused on older patients who are at higher risk. - K. Gary Barnette(CSO)

Contradiction Point 4

Choice of GLP-1 Receptor Agonist for PLATEAU Study

It involves the choice of GLP-1 receptor agonist for the PLATEAU study, which could impact the study's design, outcomes, and potential regulatory approval.

Will GLP-1 agents be allowed during PLATEAU, or will it be limited to tirzepatide only? - William Wood (B. Riley Securities)

2025Q4: We have to pick one GLP-1 receptor agonist for the study, either semaglutide or tirzepatide. The choice depends on which company we can secure for collaboration. - Mitchell Steiner(CEO)

How are you accounting for differences in lean mass loss between semaglutide and tirzepatide in the trial design? - Unidentified Analyst (H.C. Wainwright)

2025Q2: We have not found significant differences in lean mass loss between semaglutide and tirzepatide in the available data. We will stratify subjects based on the GLP-1 type for accurate comparison. - Mitchell Steiner(CEO)

Contradiction Point 5

Phase III Trial Size and Dose Decisions

It involves the expected size and dose decisions for the Phase III trial, which could impact the study's feasibility, cost, and potential regulatory approval.

With the PLATEAU study outcomes, will there be flexibility in regulatory discussions on weight loss and muscle function? - Rohan Mathur (Oppenheimer & Co.)

2025Q4: The Phase IIb PLATEAU study will be designed as a mini Phase III. We're focusing on incremental weight loss as the primary endpoint. - Mitchell Steiner(CEO)

What are the criteria for success in the Phase 2b extension maintenance study, and when will Phase 3 study data be released, including expected size and dose decisions? - Gary Nachman (Raymond James)

2025Q2: For Phase 3, it will be a 24-week study with approximately 400 patients, 200 per arm, likely using a 3 mg dose. - Mitchell Steiner(CEO)