ProfoundBio Presents Promising Data on ADC Programs, Including Early Clinical Results of Rinatabart Sesutecan in Ovarian and Endometrial Cancers, at SITC 2023

— Rina-S, a folate receptor-alpha-(FRα)-directed ADC, demonstrated encouraging anti-tumor activity in heavily pretreated patients with ovarian and endometrial cancer —

— Responses were observed across the full spectrum of FRα expression —

— Rina-S was well-tolerated at dose levels where objective responses were observed —

— Additional preclinical data support the therapeutic potential of PRO1107, a PTK7-directed ADC progressing into clinical development —

SEATTLE--(BUSINESS WIRE)--ProfoundBio, a clinical-stage biotechnology company developing novel antibody-drug conjugate (ADC) therapeutics for cancer, today announced multiple data presentations at the Society for Immunotherapy of Cancer’s 38th Annual Meeting (SITC 2023). The company shared initial results from the dose escalation portion of an ongoing Phase 1/2 trial of its lead ADC candidate, rinatabart sesutecan (Rina-S; PRO1184), as well as preclinical data on its Protein Tyrosine Kinase 7 (PTK7)-directed ADC PRO1107 and its continued ADC platform innovations.

“We are thrilled to present proof-of-concept data from our novel sesutecan ADC platform with the initial clinical results for Rina-S,” said ProfoundBio Chief Medical Officer Naomi Hunder, M.D. “We believe Rina-S’s encouraging Phase 1 activity and safety data are differentiated within the landscape of emerging targeted therapies for ovarian and endometrial cancers, as Rina-S elicited robust responses at well-tolerated doses in heavily pretreated patients, including in tumors expressing low levels of FRα. These data validate our platform and approach to developing ADCs with the potential for meaningfully improved outcomes for patients.”

Abstract #708: A Phase 1/2 Study of Rinatabart Sesutecan (PRO1184), a Novel Folate Receptor Alpha-Directed Antibody-Drug Conjugate, in Patients with Locally Advanced and/or Metastatic Solid Tumors

Presented by Justin A. Call, M.D., of START Mountain Region, West Valley City, UT, on Saturday, November 4, 2023, Exhibit Halls A and B1, 9 a.m. to 8:30 p.m. PDT

Rina-S is an investigational folate receptor-alpha-(FRα)-directed ADC based on a novel topoisomerase-1 linker-drug currently in Phase 1/2 development for a number of solid tumors. Key findings from initial Phase 1 clinical results of the Rina-S trial include data from 36 patients treated at dose levels from 60 mg/m² to 180 mg/m² administered every 21 days.

• Enrolled patients had the following tumor types: ovarian cancer (n=17), endometrial cancer (n=9), breast cancer (n=3), non-small cell lung cancer (n=5), and mesothelioma (n=2).
• Patients in the study were heavily pretreated with a median of 4.5 prior therapies; patients with ovarian cancer had a median of 6 prior therapies and patients with endometrial cancer had a median of 4 prior therapies.

Safety and activity highlights include:

• Rina-S was well tolerated at doses from 60 mg/m² to 120 mg/m², with 140 mg/m² still under evaluation as a potential maximum tolerated dose; the most common treatment-related adverse events (TRAEs) included cytopenias, gastrointestinal adverse events, and fatigue and were both reversible and manageable. Most TRAEs were Grade 1 or 2.
• No interstitial lung disease, pneumonitis, infusion-related reactions, or corneal toxicity were observed.
• Among 21 response-evaluable patients with ovarian and endometrial cancer, unselected for FRα expression, an initial objective response rate of 38% was observed (1 complete response (CR), 7 partial responses (PR)); an additional 9 patients had stable disease (SD), including 7 with decreasing tumor measurements, for a disease control rate (CR+PR+SD) of 81%.
• Antitumor activity was seen across the full spectrum of FRα expression, with objective responses observed in 8 out of 12 (67%) response-evaluable patients with ovarian and endometrial cancer having >1% FRα expression in their tumors, including 3 PRs in 3 patients with FRα expression below 25% 1+ IHC staining intensity.
• Responses were observed across a wide dose range from 60 to 140 mg/m²_, with responses deepening over time for most patients.
  • One patient with ovarian cancer had prior treatment with mirvetuximab soravtansine (Elahere™) and had a CR after receiving two doses of Rina-S.

Additional patients are being evaluated in Part A and Part B at multiple dose levels to further optimize the dose.

LD343 Platform and PRO1107 Preclinical Data Presentations, and PRO1160 Trial-In-Progress Presentation:

Abstract #1407: Expanding the Therapeutic Index of MMAE-Based Antibody-Drug Conjugates (ADCs) with a Novel Linker System (LD343)

Presented by Zhu Chen, Ph.D., ProfoundBio Chief Scientific Officer, on Friday, November 3, 2023, Exhibit Halls A and B1, 9 a.m. to 7:00 p.m. PDT

Data from ADCs incorporating ProfoundBio’s novel LD343 platform (a next-generation hydrophilic MMAE-based linker-drug) at a homogeneous drug-to-antibody ratio of 8 (DAR8) compared head-to-head with DAR4 vedotin ADCs highlights the potential to widen the therapeutic index of the clinically validated payload, MMAE.

Data highlights include:

• ADCs incorporating the highly hydrophilic LD343 at DAR8 conferred improved physicochemical properties and PK/PD characteristics relative to vedotin.
• LD343 ADCs demonstrated antitumor activity in multiple tumor types, with higher in vivo potency than vedotin even at double the amount of dosed payload.
• LD343 enabled enhanced delivery of payload to tumor tissue and reduced exposure of payload in circulation.
• LD343 enabled an approximately 4-fold increase in the tolerated drug load compared to vedotin ADCs in rats.

Abstract #1406: A Novel PTK7-Directed Antibody-Drug Conjugate (ADC) PRO1107 Demonstrated Broad Antitumor Activity with a Promising Safety Profile in Preclinical Models

Presented by Zhu Chen, Ph.D., ProfoundBio Chief Scientific Officer, on Saturday, November 4, 2023, Exhibit Halls A and B1, 9 a.m. to 8:30 p.m. PDT

The poster presentation for the anti-PTK7 ADC, PRO1107, highlights preclinical data for this ADC which incorporates LD343 at DAR8.

Data highlights include:

• Superior tumor growth inhibition and tolerability relative to the precedent PTK7-directed ADC cofetuzumab pelidotin were observed in head-to-head preclinical studies.
• Enhanced preclinical antitumor activity and tolerability are believed to be attributed to PRO1107’s increased hydrophilicity and improved physicochemical properties, augmented delivery of payload to the tumor, less systemic exposure of free payload, and a robust bystander antitumor effect.
• Pharmacokinetics demonstrated PRO1107’s stability to be similar to that of the parent antibody.

Abstract #718: Phase 1/2 Study of PRO1160, a CD70-Directed Antibody-Drug Conjugate, in Patients with Advanced Solid Tumors and Hematologic Malignancies

Presented by Sharon Ma, MPH, ProfoundBio Director of Clinical Operations, on Saturday, November 4, 2023, Exhibit Halls A and B1, 9 a.m. to 8:30 p.m. PDT

The trial-in-progress poster presentation for the anti-CD70 sesutecan ADC, PRO1160, describes the currently recruiting PRO1160-001 Phase 1/2 study (NCT05721222) in patients with solid and liquid tumors.

About Rinatabart Sesutecan (Rina-S, PRO1184)

Rina-S is an ADC comprised of a folate receptor-alpha-directed antibody conjugated to sesutecan, ProfoundBio’s novel, proprietary hydrophilic exatecan-based linker-drug, LD038, at a homogeneous drug-to-antibody ratio (DAR) of 8. Exatecan is a highly potent, membrane permeable topoisomerase-1 inhibitor with strong bystander effect that has been extensively studied as a small molecule anticancer agent. Sesutecan is a highly hydrophilic stable, cleavable linker designed to mask the hydrophobicity of conjugated exatecan on the ADC, enabling high DAR and efficient delivery of the exatecan payload to tumors while maintaining favorable physicochemical and pharmacokinetic properties of the ADC.

About the PRO1184-001 trial (NCT05579366)

This is a Phase 1/2 study of PRO1184, a folate receptor-alpha-(FRα) targeted antibody-drug conjugate, to evaluate the safety, tolerability, PK, and antitumor activity of PRO1184 in patients with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma. The study consists of two parts, Part A: Dose Escalation and Part B: Dose Expansion.

About PRO1107

PRO1107 is an ADC comprised of a Protein Tyrosine Kinase 7 (PTK7)-targeted antibody conjugated to ProfoundBio’s novel, proprietary hydrophilic MMAE-based linker-drug, LD343, at a homogeneous DAR of 8. MMAE is a potent, membrane permeable microtubule inhibitor that has been clinically validated as an ADC payload by multiple vedotin-based ADCs incorporating MMAE at a DAR of 4. LD343 is a highly hydrophilic stable, cleavable linker designed to mask the hydrophobicity of conjugated MMAE on the ADC, enabling high DAR and efficient delivery of the MMAE payload to tumors while maintaining favorable physicochemical and pharmacokinetic properties of the ADC. The investigational new drug (IND) application for PRO1107 has been cleared by FDA and its Phase 1/2 clinical trial is expected to begin enrollment in early 2024.

About ProfoundBio

ProfoundBio is a clinical-stage biotechnology company focused on the development of novel antibody-based therapeutics with curative potential for patients with cancer. Built on internally developed, innovative, and proprietary technology platforms, ProfoundBio has developed a pipeline consisting of multiple antibody-drug conjugate (ADC) drug candidates targeting solid tumors and hematological malignancies that are in discovery, preclinical, and clinical development stages. The company’s clinical stage programs are rinatabart sesutecan (Rina-S; PRO1184), an ADC targeting folate receptor-alpha, PRO1160, an ADC targeting CD70, and PRO1107, an ADC targeting PTK7. ProfoundBio is headquartered in Seattle, Washington.

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