On July 30, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported a poster (display) presentation of clinical data from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo) at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 taking place in Barcelona, Spain on September 13-17, 2024 (Press release, MacroGenics, JUL 30, 2024, View Source [SID1234645162]).

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The abstract submitted to ESMO (Free ESMO Whitepaper) was based on an April 12 data cut off, and the poster will report additional data from a July 9 data cut-off, including safety, efficacy and landmark 6-month radiographic progression-free survival (rPFS) data. The poster is titled:

1654P; TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)

"We are pleased to have the opportunity to present updated safety and efficacy data from our TAMARACK trial at the upcoming ESMO (Free ESMO Whitepaper) Congress in September," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We believe that these data will give us valuable insights to inform potential next steps for the vobra duo program in mCRPC, and we look forward to providing additional perspective to the investment community following our ESMO (Free ESMO Whitepaper) presentation."

In accordance with ESMO (Free ESMO Whitepaper)’s embargo policy, the poster will be published under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source on or around September 15, 2024. Given the embargoed TAMARACK data, the Company’s management has entered a quiet period and will not be hosting a conference call to discuss its financial results or corporate progress for the quarter ended June 30, 2024. The Company expects to issue a release detailing its financial results and corporate progress on or around August 6, 2024, and plans to host an investor conference call following the ESMO (Free ESMO Whitepaper) presentation to discuss the TAMARACK data and potential next steps for the vobra duo program.

TAMARACK Study Update

MacroGenics completed enrollment of the TAMARACK study in the fourth quarter of 2023, and plans to present at ESMO (Free ESMO Whitepaper) the study’s landmark primary endpoint of 6-month rPFS rate, which represents the proportion of study participants who remain alive and progression-free at 6 months.

In late July 2024, after a review of accumulated study data, MacroGenics agreed with the study’s Independent Data Monitoring Committee’s (IDMC) recommendation that study treatment should be discontinued for the remaining mCRPC study participants who potentially could have received additional doses. Most of these remaining study participants had already received 8-12 cycles of vobra duo. Participants continue to be monitored for adverse events, disease progression and survival.

"Patient safety is our top priority, and having reached the study’s primary endpoint, we decided to discontinue additional dosing for the remaining TAMARACK participants who had not yet completed treatment. We expect to have the data necessary to determine next steps for the vobra duo program later this year and will provide further updates on an investor call following our ESMO (Free ESMO Whitepaper) presentation," continued Dr. Koenig. "We are committed to fully assessing the potential of vobra duo in mCRPC through rigorous evaluation of the data, including the mature median rPFS and OS. We look forward to completing follow-up for the TAMARACK trial before year-end and presenting final data at a future conference."

The Company expects to have the mature efficacy findings, including median rPFS, later in the second half of 2024 and plans to present the data at a subsequent medical conference. The data to be presented at ESMO (Free ESMO Whitepaper) will be used to inform how future potential studies could be designed.

About Vobra Duo and the TAMARACK Study

Vobra duo is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. The TAMARACK Phase 2 study of vobra duo is being conducted in participants with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W).

On July 30, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported the achievement of $100 million in milestones from Incyte Corporation related to development progress of ZYNYZ (retifanlimab-dlwr), following an agreement on July 24, 2024, pursuant to which certain milestones were deemed to have been met (Press release, MacroGenics, JUL 30, 2024, View Source [SID1234645160]). ZYNYZ is an intravenous PD-1 inhibitor indicated in the U.S. for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma. ZYNYZ is a monoclonal antibody initially developed by MacroGenics and licensed to Incyte under a 2017 exclusive global collaboration and license agreement. Incyte and its collaborators continue to pursue development of retifanlimab in other indications, which include both monotherapy and combination regimens.

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Under the 2017 collaboration agreement with Incyte, MacroGenics received an upfront payment of $150 million and has achieved a total of $215 million in milestones, including the recent $100 million described above. MacroGenics remains eligible to receive up to a total of $210 million in potential development and regulatory milestones and up to $330 million in potential commercial milestones. MacroGenics receives tiered royalties, which range from 15 to 24 percent, on worldwide net sales of ZYNYZ.

MacroGenics expects to provide its June 30, 2024 cash, cash equivalents and marketable securities balance in its second quarter earnings announcement on or around August 6, 2024. The Company currently anticipates that its June 30, 2024 cash balance plus the $100 million in milestones achieved from Incyte, in addition to projected and anticipated future payments from partners and product revenues should support its cash runway into 2026. The Company’s expected funding requirements reflect anticipated expenditures related to its ongoing clinical and preclinical studies.

On July 30, 2024 Incyte (Nasdaq:INCY) reported 2024 second quarter financial results, and provides a status update on the Company’s clinical development portfolio (Press release, Incyte, JUL 30, 2024, View Source [SID1234645157]).

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"In the second quarter of 2024, total revenues grew 9% year-over-year, surpassing $1.0 billion for the quarter. The commercial performance during this period was driven by strong patient demand for Opzelura (ruxolitinib) and growth across all indications for Jakafi (ruxolitinib)," said Hervé Hoppenot, Chief Executive Officer, Incyte. "In R&D, we completed a strategic review of our pipeline and have further intensified our focus on clinical programs that we believe can be transformational for patients. The $2.0 billion share repurchase completed during the second quarter, underscores our confidence in our commercial portfolio, clinical pipeline and Incyte’s long-term value."

Transformation of Pipeline

•Incyte announces a strategic review of its pipeline with an increased focus on high potential impact programs including, but not limited to:
◦IAI/Dermatology: povorcitinib and MRGPRX2 and MRGPRX4, which were recently acquired from Escient Pharmaceuticals
◦MPNs/GVHD: mCALR, JAK2V617Fi, BETi, and ALK2i
◦Oncology: CDK2i, KRASG12Di and TGFßR2×PD-1
•The Company will discontinue further development of both oral, small molecule PD-L1 inhibitors, as well as LAG-3 monoclonal antibody, TIM-3 monoclonal antibody and LAG-3xPD-1 bispecific.
1

Recent Company Updates
•Incyte announces positive topline results from two Phase 3 clinical studies evaluating retifanlimab (Zynyz), a humanized monoclonal antibody targeting programmed cell death receptor-1 (PD-1), in squamous cell anal carcinoma (SCAC) and non-small cell lung cancer (NSCLC). The Phase 3 PODIUM-303 study in SCAC met its primary endpoint of progression free survival and the Phase 3 PODIUM-304 study in NSCLC met its primary endpoint of overall survival. The safety analysis from both studies demonstrated that retifanlimab was generally well-tolerated with no new safety signals observed. Incyte plans to share the Phase 3 data from both studies in the second half of 2024. POD1UM-303 is a Phase 3, global, multicenter, randomized, double-blind study evaluating carboplatin-paclitaxel with retifanlimab or placebo in patients with inoperable locally recurrent or metastatic SCAC who have not previously been treated with chemotherapy. POD1UM-304 is a Phase 3, global, multicenter, randomized, double-blind study evaluating platinum-based chemotherapy with retifanlimab or placebo in patients with first-line, metastatic squamous or nonsquamous NSCLC.
•In June 2024, Incyte repurchased a total of 33,325,849 shares of its common stock at a price of $60.00 per share, for a total cost of approximately $2.0 billion, excluding fees and expenses. These shares represented approximately 14.8 percent of the Company’s total outstanding shares of common stock as of June 7, 2024.
•In May 2024, Incyte announced it completed the acquisition of Escient Pharmaceuticals, a clinical-stage drug discovery and development company advancing novel small molecule therapeutics for systemic immune and neuro-immune disorders. Under the terms of the agreement, Incyte acquired Escient and its clinical development portfolio, including EP262, a first-in-class, potent, highly selective, once-daily small molecule antagonist of Mas-related G protein-coupled receptor (MRGPRX2) and EP547, a first-in-class oral MRGPRX4 antagonist.
•In April 2024, Incyte and China Medical System Holdings Limited announced the Companies entered into a Collaboration and License Agreement, through a wholly-owned dermatology medical aesthetic subsidiary CMS Skinhealth, for the development and commercialization of povorcitinib, a selective oral JAK1 inhibitor, in Mainland China, Hong Kong, Macau, Taiwan Region and eleven Southeast Asian countries.
Jakafi:
Net product revenues for the second quarter 2024 of $706 million (+3% Y/Y):
▪Paid demand increased 9% in the second quarter of 2024 versus the same quarter in the prior year, with growth across all indications.
▪Year over year net product revenue growth was lower than paid demand growth due to higher channel inventory levels at the end of the second quarter of 2023 versus the same period of 2024. Channel inventory at the end of the second quarter of 2024 was within the normal range.
Opzelura:
Net product revenues for the second quarter 2024 of $122 million (+52% Y/Y):
▪Net product revenues growth in the second quarter of 2024 were driven by patient demand, refills and expansion in payer coverage in both atopic dermatitis (AD) and vitiligo.
▪Net product revenues of $11 million in the second quarter of 2024 in Europe. Incyte achieved full reimbursement in Spain and Italy at the end of the second quarter 2024 and in France in July 2024.
Additional Pipeline Updates
Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights
▪Combination trials of ruxolitinib twice daily (BID) with zilurgisertib and BETi are ongoing and continue to enroll. A Phase 3 study for BETi is expected to advance into Phase 3 with an expected update later this year. Clinical proof-of-concept for zilurgisertib is anticipated in the second half of 2024.
▪The Phase 1 studies evaluating mCALR and JAK2V617Fi are ongoing and enrolling patients. Initial data for both studies is anticipated in 2025.
2

MPN and GVHD Programs Indication and status
Ruxolitinib XR (QD)
(JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD
Ruxolitinib + zilurgisertib
(JAK1/JAK2 + ALK2i) Myelofibrosis: Phase 2
Ruxolitinib + INCB57643
(JAK1/JAK2 + BETi) Myelofibrosis: Phase 2
Axatilimab (anti-CSF-1R)1
Chronic GVHD: Pivotal Phase 2 (third-line plus therapy) (AGAVE-201); BLA under review in the U.S.
Ruxolitinib + axatilimab1
(JAK1/JAK2 + anti-CSF-1R)
Chronic GVHD: Phase 2 in preparation
Steroids + axatilimab1
(Steroids + anti-CSF-1R)
Chronic GVHD: Phase 3 in preparation
INCA33989
(mCALR) Myelofibrosis, essential thrombocythemia: Phase 1
INCB160058
(JAK2V617Fi) Phase 1

1 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals.
Other Hematology/Oncology – key highlights
Heme/Oncology Programs Indication and status
Pemigatinib (Pemazyre)
(FGFR1/2/3)
Myeloid/lymphoid neoplasms (MLN): approved in the U.S. and Japan
Cholangiocarcinoma (CCA): Phase 3 (FIGHT-302)
Tafasitamab (Monjuvi/Minjuvi)
(CD19)
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Phase 3 (B-MIND)
First-line DLBCL: Phase 3 (frontMIND)
Relapsed or refractory follicular lymphoma (FL) and relapsed or refractory marginal zone lymphoma (MZL): Phase 3 (inMIND)
Retifanlimab (Zynyz)1
(PD-1)
Merkel cell carcinoma (MCC): approved in the U.S. and Europe
Squamous cell anal cancer (SCAC): Phase 3 (POD1UM-303)
Non-small cell lung cancer (NSCLC): Phase 3 (POD1UM-304)
MSI-high endometrial cancer: Phase 2 (POD1UM-101, POD1UM-204)
INCB123667
(CDK2i) Solid tumors with Amplification/ Overexpression of CCNE1: Phase 1
INCB161734
(KRASG12D) Advanced metastatic solid tumors with a KRAS G12D mutation: Phase 1
INCA33890
(TGFßR2×PD-1)2
Advanced or metastatic solid tumors: Phase 1

1 Retifanlimab licensed from MacroGenics.
2 Development in collaboration with Merus.
Inflammation and Autoimmunity (IAI) – key highlights
Dermatology
Opzelura
▪In March 2024, Incyte presented data at the 2024 AAD Annual Meeting from its randomized, placebo-controlled, Phase 2 study evaluating the safety and efficacy of ruxolitinib cream (Opzelura) in adults with mild/moderate hidradenitis suppurativa (HS). At Week 16, patients receiving ruxolitinib cream 1.5% twice daily (BID) had significantly greater decreases from baseline versus placebo in total abscess and inflammatory nodule (AN) count, the primary endpoint of the study. The overall safety profile of ruxolitinib cream was consistent with previous data, and no new safety signals were observed. A Phase 3 study is expected to initiate in 2025.
3

▪Ruxolitinib cream in other indications: Phase 2 studies in lichen planus and lichen sclerosus have completed enrollment. Two Phase 3 trials evaluating ruxolitinib cream in prurigo nodularis (PN) are ongoing.
Povorcitinib (INCB54707)
▪The Phase 2, randomized, double-blind, placebo-controlled, dose ranging study evaluating the efficacy and safety of povorcitinib in participants with PN were presented at the 2024 AAD Annual Meeting with the study meeting its primary and secondary endpoints following 16 weeks of treatment across all dosing groups, reinforcing povorcitinib’s potential role in treating PN. A Phase 3 study in PN is expected to initiate in 2024.
▪Two Phase 2 trials in asthma and chronic spontaneous urticaria are enrolling.
IAI and Dermatology Programs Indication and status
Ruxolitinib cream (Opzelura)1
(JAK1/JAK2)
Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3)
Vitiligo: Approved in the U.S. and Europe
Lichen planus: Phase 2
Lichen sclerosus: Phase 2
Hidradenitis suppurativa: Phase 2; Phase 3 expected to initiate in 2025
Prurigo nodularis: Phase 3 (TRuE-PN1, TRuE-PN2)
Ruxolitinib cream + UVB
(JAK1/JAK2 + phototherapy) Vitiligo: Phase 2
Povorcitinib
(JAK1) Hidradenitis suppurativa: Phase 3 (STOP-HS1, STOP-HS2)
Vitiligo: Phase 3 (STOP-V1, STOP-V2)
Prurigo nodularis: Phase 3 expected to initiate in 2024
Asthma: Phase 2
Chronic spontaneous urticaria: Phase 2
INCB000262 (EP262)
(MRGPRX2) Chronic spontaneous urticaria: Phase 2
Chronic inducible urticaria: Phase 1b
Atopic dermatitis: Phase 2a
INCB000547 (EP547)
(MRGPRX4) Cholestatic pruritus: Phase 2a
INCA034460
(anti-IL-15Rβ) Vitiligo: Phase 1

1 Novartis’ rights to ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis do not include topical administration.
Other
Other Program Indication and Phase
Zilurgisertib
(ALK2) Fibrodysplasia ossificans progressiva: Pivotal Phase 2

4

Partnered
Partnered Programs Indication and Phase
Ruxolitinib (Jakavi)1
(JAK1/JAK2)
Acute and chronic GVHD: Approved in Europe and Japan
Baricitinib (Olumiant)2
(JAK1/JAK2)
AD: Approved in Europe and Japan
Severe alopecia areata (AA): Approved in the U.S., Europe and Japan
Capmatinib (Tabrecta)3
(MET)
NSCLC (with MET exon 14 skipping mutations): Approved in the U.S., Europe and Japan

1 Ruxolitinib (Jakavi) licensed to Novartis ex-U.S. for use in hematology and oncology excluding topical administration.
2 Baricitinib (Olumiant) licensed to Lilly: approved as Olumiant in multiple territories globally for certain patients with moderate-to-severe rheumatoid arthritis; approved as Olumiant in EU and Japan for certain patients with atopic dermatitis.
3 Capmatinib (Tabrecta) licensed to Novartis.
2024 Second Quarter Financial Results
The financial measures presented in this press release for the three and six months ended June 30, 2024 and 2023 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers.

Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry.
As changes in exchange rates are an important factor in understanding period-to-period comparisons, Management believes the presentation of certain revenue results on a constant currency basis in addition to reported results helps improve investors’ ability to understand its operating results and evaluate its performance in comparison to prior periods. Constant currency information compares results between periods as if exchange rates had remained constant period over period. The Company calculates constant currency by calculating current year results using prior year foreign currency exchange rates and generally refers to such amounts calculated on a constant currency basis as excluding the impact of foreign exchange or being on a constant currency basis. These results should be considered in addition to, not as a substitute for, results reported in accordance with GAAP. Results on a constant currency basis, as the Company presents them, may not be comparable to similarly titled measures used by other companies and are not measures of performance presented in accordance with GAAP.

On July 30, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in late-stage development with its DNA-mediated immunotherapy, reported positive topline results from the Phase 2 OVATION 2 Study with IMNN-001 in patients with advanced ovarian cancer (Press release, IMUNON, JUL 30, 2024, View Source [SID1234645156]). OVATION 2 is a randomized study of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) inclusive of interval debulking or cytoreductive surgery compared with a control arm of standard-of-care NACT alone. IMNN-001 is the Company’s interleukin-12 (IL-12) immunotherapy based on its TheraPlas technology.

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Highlights from patients treated with IMNN-001 plus standard-of-care in a first-line treatment setting include:

An 11.1 month increase in median OS compared with standard-of-care alone in the intent-to-treat population (ITT).
A hazard ratio in the ITT population of 0.74, which indicates a 35% improvement in survival.
Among the approximately 90% of trial participants who received at least 20% of specified treatments per-protocol in both study arms, patients in the IMNN-001 arm had a 15.7 month increase in median OS, representing a further extension of life with a hazard ratio of 0.64, a 56% improvement in survival.
For the nearly 40% of trial participants treated with a poly ADP-ribose polymerase (PARP) inhibitor, the hazard ratio decreased further to 0.41, with median OS in the IMNN-001 treatment arm not yet reached at the time of database lock, compared with median OS of 37.1 months in the standard-of-care treatment arm.
The PFS results, the trial’s primary endpoint, support the OS results with:

A three-month improvement in PFS compared with standard-of-care alone.
A hazard ratio in the intent-to-treat population of 0.79, indicating a 27% improvement in delaying progression for the IMNN-001 treatment arm.
"These strong and clinically meaningful Phase 2 results are highly encouraging, suggesting that IMNN-001 may improve the outcomes for women with advanced ovarian cancer. In the near term, we look forward to advancing our therapeutic into a Phase 3 pivotal study as soon as possible," said Stacy Lindborg, Ph.D., President and Chief Executive Officer of IMUNON. "Advancements in treatment options for advanced ovarian cancer in women who require neoadjuvant treatment have been limited over the years, and these patients continue to have poor prognoses. Our goal is for IMNN-001 to play an important role in the treatment regimen for the more than 300,000 women diagnosed with this deadly disease. On behalf of IMUNON, I extend heartfelt thanks to the women who participated in this trial, their families and the investigators."

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with NACT of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT.

As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

Sebastien Hazard, M.D., Chief Medical Officer of IMUNON, added, "It is highly gratifying to witness the extraordinary overall survival benefit that IMNN-001 showed in this Phase 2 study further supported by consistency across data, including in progression-free survival and in the patients who received three doses or more of IMNN-001 gaining an additional 15.7 months of life, while the safety profile was tolerable. It suggests that IMUNON’s IL-12 gene therapy has a long-term impact on the disease."

Commenting on the study results, Premal H. Thaker, M.D, Interim Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, and the OVATION 2 Study Chair, said, "Typically an increase in survival of six months is considered to be clinically meaningful, and extending survival from 29 months with standard-of-care treatment to 40 months with the addition of IMNN-001 is compelling. Importantly, the extension of survival among IMNN-001 patients also exposed to the new standard that includes PARP inhibitors is even greater. If confirmed in a Phase 3 clinical trial, IMNN-001 could reset the standard of care for women with ovarian cancer."

Charles A. "Trey" Leath, III, M.D., Director, Division of Gynecologic Oncology, Ellen Gregg Shook Culverhouse Chair in Gynecologic Oncology, Professor, Department of Obstetrics and Gynecology at University of Alabama Medical Center, and OVATION 2 Principal Investigator, said, "I (We) have been investigating IMNN-001 since the Phase 1 OVATION 1 Study and continue to be frustrated by the lack of substantial progress in primary treatment options available to treat this disease. The results from this trial demonstrating that IMNN-001 could extend life by one year or longer are provocative and powerful. I believe that should efficacy be confirmed in a pivotal study, IMNN-001 will be quickly incorporated into the care regimen."

IMUNON plans to hold an End-of-Phase 2 meeting with the U.S. Food and Drug Administration as soon as possible to discuss the protocol for a Phase 3 study, which is anticipated to begin in the first quarter of 2025. IMUNON also plans to present full OVATION 2 Study results at an upcoming medical conference and to submit the results for publication in a peer-reviewed medical journal.

Conference Call and Webcast

IMUNON is hosting a conference call at 8:30 a.m. Eastern time today to discuss OVATION 2 Study results, next steps and to answer questions. Dr. Thaker will be joining management on the call. To participate in the conference call, please dial 833-816-1132 (Toll-Free/North America) or 412-317-0711 (International/Toll) and ask for the IMUNON call. A live webcast of the call will be available here.

Participants are encouraged to preregister for the call here.

The call will be archived for replay through August 13, 2024. The replay can be accessed at 877-344-7529 (U.S. Toll-Free), 855-669-9658 (Canada Toll-Free) or 412-317-0088 (International Toll), using the replay access code 7783601. A webcast of the call will be available here for 90 days.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On July 30, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported topline results from two late-stage trials evaluating the efficacy and safety of pamrevlumab in patients with pancreatic cancer and a corporate update (Press release, FibroGen, JUL 30, 2024, View Source [SID1234645155]).

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The pamrevlumab experimental arm in PanCAN’s Precision Promise Phase 2/3 adaptive platform trial compared treatment with pamrevlumab combined with gemcitabine + nab-paclitaxel to gemcitabine + nab-paclitaxel alone for treatment in first line (1L) and second line (2L) patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The pamrevlumab arm of the study did not meet the primary endpoint of overall survival as determined by the protocol pre-specified Bayesian statistical analysis.

The Phase 3 LAPIS trial compared treatment with pamrevlumab combined with gemcitabine + nab-paclitaxel or FOLFIRINOX to placebo combined with gemcitabine + nab-paclitaxel or FOLFIRINOX for the treatment of locally advanced, unresectable pancreatic cancer (LAPC). The study did not meet the primary endpoint of overall survival.

"We are deeply disappointed that the pamrevlumab arm in the Precision Promise trial and the LAPIS trial did not meet the primary endpoint of overall survival," said Thane Wettig, Chief Executive Officer, FibroGen. "We were hopeful that pamrevlumab could bring meaningful innovation to pancreatic cancer patients in desperate need of new therapies. FibroGen would like to thank the patients, their families and the clinical trial investigators and teams for their dedication to participating in these studies. I would also like to express my deepest gratitude to our FibroGen colleagues who have dedicated so much of their time and energy for the prospect of bringing much needed therapies to some of the most challenging and deadly diseases affecting humanity."

Based upon the results of the late-stage pamrevlumab trials in pancreatic cancer, the Company plans to implement an immediate and significant cost reduction plan in the U.S. The pamrevlumab development program will be terminated and the Company plans to expeditiously wind down any remaining pamrevlumab obligations. As a result of the cost reduction plan, headcount in the U.S. will be reduced by approximately 75%.

FibroGen’s collaboration agreement with AstraZeneca for roxadustat in China, where roxadustat is the market leader by brand value share in the chronic kidney disease (CKD) anemia category, as well as FibroGen’s collaboration agreement with Astellas for roxadustat in the E.U., Japan, and other territories, remain in place.

PanCAN’s Precision Promise Pamrevlumab Arm Efficacy Results

Given both 1L and 2L pamrevlumab treatment groups graduated into Stage 2 of PanCAN’s Precision Promise study, the hazard ratio for the primary overall survival (OS) analysis assumed a common hazard ratio to estimate a single treatment effect for both 1L and 2L pamrevlumab patients combined compared to patients treated with gemcitabine + nab-paclitaxel. In addition, the pre-specified Bayesian model utilized a hierarchical model that included the borrowing of data from the mFOLFIRINOX control arm to the gemcitabine + nab-paclitaxel control arm for the primary efficacy analysis. The pre-specified primary efficacy analysis was performed in a modified intention-to-treat (mITT) population that included only subjects who initiated treatment. The mITT population in the pamrevlumab arm was comprised of a total of 102 patients in the 1L treatment group and 111 patients in the 2L treatment group and the gemcitabine + nab-paclitaxel control arm was comprised of a total of 34 patients in the 1L treatment group and 36 patients in the 2L treatment group.

Primary OS Analysis as Determined by Pre-Specified Bayesian Statistical Analysis (mITT Population)

Bayesian Model Common Hazard Ratio (HR) Posterior Probability
Median Mean (SD) 95% CI Pr(HR < 1)
Primary Efficacy Analysis 1.170 1.184 (0.175) (0.882, 1.563) 0.13977
LAPIS Efficacy Results

The study did not meet the primary endpoint of overall survival (stratified log-rank p-value=0.55). Median overall survival of 17.3 months was observed in the pamrevlumab combined with gemcitabine + nab-paclitaxel or FOLFIRINOX arm compared to median overall survival of 17.9 months in the control arm of placebo combined with gemcitabine + nab-paclitaxel or FOLFIRINOX (HR: 1.08; 95% CI – 0.83 to 1.41).

Pamrevlumab Safety Results (Precision Promise and LAPIS)

The preliminary safety analyses across both studies indicate that the safety profile of pamrevlumab combined with gemcitabine + nab-paclitaxel or FOLFIRINOX was generally well tolerated with an acceptable safety profile in pancreatic cancer patients. No clinically meaningful differences in treatment emergent adverse events were seen between the treatment arms.

About PanCAN’s Precision Promise
PanCAN’s Precision Promise adaptive platform trial (NCT04229004) is a U.S.-based, seamless Phase 2/3 study sponsored by PanCAN that enrolled patients in 24 sites nationwide. The multi-arm study consists of experimental treatment arms and two comparator arms: gemcitabine + nab-paclitaxel and mFOLFIRINOX. The pamrevlumab experimental arm enrolled 102 patients with mPDAC in first line (1L) and 111 patients with mPDAC in second line (2L). Both 1L and 2L patients received pamrevlumab in combination with gemcitabine and nab-paclitaxel. The final analysis was based upon the data collected up to 12 months after the last patient initiated treatment.

About LAPIS
The LAPIS study is a global Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine + nab-paclitaxel or FOLFIRINOX in the treatment of participants with locally advanced, unresectable pancreatic cancer (LAPC). The study enrolled 284 patients, who were randomized at a 1:1 ratio to receive either pamrevlumab or placebo, in combination with either gemcitabine + nab-paclitaxel or FOLFIRINOX. All patients were dosed up to six cycles of treatment and patients who completed study treatment were evaluated for surgical exploration for possible R0 or R1 resection. Participants who were ineligible for surgical exploration continued to receive treatment as per standard of care (SOC) for each institution.

About Pamrevlumab
Pamrevlumab is a potential first-in-class anti-CTGF fully human monoclonal antibody being developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF). Pamrevlumab is in clinical development for the treatment of metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer (LAPC). The U.S. Food and Drug Administration has granted Orphan Drug Designation for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC), and Fast Track designation to pamrevlumab for the treatment of patients with LAPC. Pamrevlumab is an investigational drug and not approved for marketing by any regulatory authority. For information about our pamrevlumab studies please visit www.clinicaltrials.gov.