FGEN FibroGen Inc

FibroGen, Inc. (NASDAQ: FGEN) today announced topline data from the Fortis Therapeutics-sponsored Phase 1 study of FG-3246 (also known as FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with an MMAE-containing payload, in a dose-escalation and dose-expansion trial enrolling patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors have progressed on at least one androgen receptor-signaling inhibitor (ARSI).

“We are delighted to showcase the latest encouraging clinical data from the FOR46-001 Phase 1 ADC trial,” said Deyaa Adib, M.D., Chief Medical Officer of FibroGen. “We observed a median radiographic progression free survival of 8.7 months in heavily pre-treated patients, who received biologically active doses of FG-3246 in the second line or later setting prior to chemotherapy. These Phase 1 data provide evidence of a favorable safety profile and promising clinical activity as further evidenced by prostate-specific antigen reduction of ≥ 50% and shrinking of measurable disease. We look forward to publishing the totality of the Phase 1 data as we advance the program further in the clinic.”

In the Phase 1 dose-escalation portion of the study, ascending dose levels of FG-3246 were administered every 3 weeks. In the dose-expansion arm of the trial, patients were treated at the 2.7 mg/kg adjusted body weight dosing (AjBW) until disease progression. The endpoints were safety, tolerability, and anti-tumor activity as measured by the decline of prostate-specific antigen (PSA) from baseline, objective tumor response rate in patients with measurable disease, and radiographic progression free survival (rPFS).

The completed Phase 1 trial includes a total of 56 patients from the dose-escalation and dose-expansion cohorts. The efficacy analysis includes patients who received a starting dose of FG-3246 of ≥ 1.2 mg/kg in the dose-escalation cohort, and patients who received 2.7 mg/kg AjBW with a histologic diagnosis of adenocarcinoma in the dose-expansion cohort. Patients were heavily pre-treated, having received a median of 5 lines of therapy prior to receiving FG-3246.

In the efficacy analysis, PSA reductions of ≥ 50% were observed in 36% of PSA evaluable patients. For RECIST evaluable patients, 20% met the criteria of a partial response, or tumor reduction in size of ≥ 30%, with a median duration of response of 7.5 months. The median rPFS in this heavily pre-treated patient population was 8.7 months.

The most frequent adverse events were consistent with other MMAE-based ADCs and included infusion related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy.

“The results from the FOR46-001 Phase 1 study are promising, demonstrating a manageable safety profile and continued robust signals of clinical activity,” stated Dr. Rahul Aggarwal, Professor of Medicine at University of California San Francisco and Lead Investigator of the study. “The observed median radiographic progression free survival of 8.7 months in patients treated with a starting FG-3246 dose of 1.2 mg/kg and higher is quite favorable and highlights the therapeutic potential of FG-3246 as a new ADC aimed at a novel target. These findings warrant further investigation and hold promise for addressing the therapeutic needs of patients with CD46 positive prostate cancer. We are also excited about potential combinations with FG-3246 and will be presenting investigator sponsored trial data of FG-3246 in combination with enzalutamide at the upcoming ASCO 2024 annual meeting.”

Earlier data from the FOR46-001 trial had been presented at the American Society for Clinical Oncology (ASCO) 2022 annual meeting1, and complete results from the study are being submitted to a medical journal for publication in 2024.

About the Phase 1 StudyFOR46-001 (NCT03575819) is a Phase 1, dose-escalation study to evaluate multiple doses of IV-administered FG-3246 (also known as FOR46) in patients with mCRPC who have progressive disease on at least one ARSI, followed by a dose-expansion cohort, to evaluate the safety, tolerability, PK, biological activity, and preliminary evidence of anti-tumor activity of FG-3246 in this patient population.

Thirty-three (33) patients were enrolled in the dose-escalation phase of the study at doses between 0.1 mg/kg and 3.0 mg/kg every three weeks (Q3W), with adjusted body weight dosing (AjBW) used at most dose levels above 2.1 mg/kg. Safety and tolerability of FG-3246 were evaluated in the dose-escalation period of the study.

Twenty-three (23) patients were enrolled in the dose-expansion period of the study; 18 patients with adenocarcinoma mCRPC (Cohort 1) and five patients with neuroendocrine prostate cancer (Cohort 2). All patients in the expansion cohorts were treated at 2.7 mg/kg AjBW to a maximum of 270 mg every three weeks.

The safety profile of FG-3246 was characterized, and anti-tumor activity of FG-3246 in adenocarcinoma patients dosed at ≥ 1.2 mg/kg was evaluated.

About Metastatic Castration-Resistant Prostate CancerProstate cancer develops when malignant cells form and grow in the prostate gland. Prostate cancer is the most common cancer in men in the United States, who currently have a 1 in 8 lifetime risk of developing the disease.2 Approximately 290,000 new diagnoses of prostate cancer and nearly 35,000 deaths were estimated in the U.S. in 2023.2 Metastatic castration-resistant prostate cancer (mCRPC) is a form of advanced prostate cancer that shows signs of growth, even with low levels of testosterone.2 With mCRPC, the cancer stops responding to hormone therapies and can be life-threatening if it spreads to other parts of the body such as nearby lymph nodes, bones, the bladder, rectum, liver, lungs, and the brain. Death from prostate cancer is typically the result of mCRPC, with a 5-year survival rate of 34%3, and the unfortunate reality remains that mCRPC is an incurable disease.4

About FG-3246FG-3246 (also known as FOR46) is a potential first-in-class fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and other tumor types. FG-3246 binds to an epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types, and demonstrates very limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing Phase 1/2 study being conducted at UCSF to evaluate it in combination with enzalutamide with initial data expected in mid-2024, and a biomarker trial using a PET biomarker for CD46 using the same antibody backbone. We anticipate the initiation of the Phase 2 trial in metastatic castration-resistant prostate cancer in the second half of 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.

About FibroGen FibroGen, Inc. is a biopharmaceutical company focused on accelerating the development of novel therapies at the frontiers of cancer biology. Pamrevlumab, a fully human anti-CTGF monoclonal antibody, is in clinical development for the treatment of metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer (LAPC). Roxadustat (爱瑞卓®, EVRENZOTM) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted for review by the China Health Authority. FG-3246 (also known as FOR46), a first-in-class antibody-drug conjugate (ADC) targeting CD46 is in development for the treatment of metastatic castration-resistant prostate cancer. This program also includes the development of an associated CD46-targeted PET biomarker. In addition, FibroGen has expanded its research and development portfolio to include two immuno-oncology product candidates for the treatment of solid tumors. For more information, please visit www.fibrogen.com.

Forward-Looking Statements This release contains forward-looking statements regarding FibroGen’s strategy, future plans and prospects, including statements regarding its clinical programs and those of its collaboration partner Fortis, and UCSF. These forward-looking statements include, but are not limited to, statements regarding the efficacy, safety, and potential success of FibroGen product candidates, and statements about FibroGen’s plans and objectives and typically are identified by use of terms such as “may,” “will,” “should,” “on track,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. FibroGen’s actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of its various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in FibroGen’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, as filed with the Securities and Exchange Commission (SEC), including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and FibroGen undertakes no obligation to update any forward-looking statement in this press release, except as required by law.

References: 1. Aggarwal, R. et al. Journal of Clinical Oncology 2022 40:16_suppl, 3001-30012. Schaeffer, E. et al. https://jnccn.org/view/journals/jnccn/21/10/article-p1067.xml3. Seer.cancer.gov https://seer.cancer.gov/statfacts/html/prost.html4. Dong, L. et al. Asian Journal of Urology (2019) 6, 26e41

FibroGen, Inc.

Investors:David DeLucia, CFAVice President of Corporate FP&A / Investor Relationsir@fibrogen.com

Media:Meichiel KeenanDirector, Investor Relations and Corporate Communicationsmedia@fibrogen.com