On April 24, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that the Company has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for HB-700, a novel arenaviral therapeutic vaccine for the treatment of KRAS-mutated cancers (Press release, Hookipa Biotech, APR 24, 2024, View Source [SID1234642281]).

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HOOKIPA’s HB-700 program is designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers by targeting the five most prevalent KRAS mutations in these disease indications: G12D, G12V, G12R, G12C and G13D. This program has the potential to benefit more patients than single mutation inhibitors.

The IND submission achieves a final $10 million milestone payment from Roche. Effective April 25, 2024, the Company will regain full control of the associated intellectual property portfolio and have full collaboration and licensing rights for the HB-700 program. The Company will publish preclinical data in an abstract at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting.

"We are proud to have another IND cleared for a potentially powerful oncology program. Our HB-700 program targets five KRAS-mutations found in multiple cancer indications with a single product candidate," said Joern Aldag, Chief Executive Officer at HOOKIPA. "Importantly, the submission of the IND results in us receiving a final $10 million milestone payment. We continue to define our clinical development strategy which includes the possibility of collaboration or partnership for this program."

About KRAS-mutated cancers
KRAS is a gene that acts as an on/off switch for cell growth. When there is a mutation, or error, in the gene, cells can grow out of control. KRAS mutations are among the most common mutations that cause cancer. While KRAS-mutated, tumor-specific treatments exist, there remains an opportunity to target a broader range of KRAS-mutations simultaneously and thereby potentially help more people impacted by these cancers.

About HB-700
HB-700 is an investigational arenaviral immunotherapy designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations (G12D, G12V, G12R, G12C and G13D) and may benefit more patients than single mutation inhibitors.

On April 24, 2024 GSK plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) accepted the supplemental Biologics License Application (sBLA) for Jemperli (dostarlimab) in combination with standard-of-care chemotherapy (carboplatin and paclitaxel) to expand treatment to all adult patients with primary advanced or recurrent endometrial cancer (Press release, GlaxoSmithKline, APR 24, 2024, View Source [SID1234642280]). This would include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours.

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Currently, Jemperli is FDA-approved in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is either mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).

The FDA granted Priority Review for this application and assigned a Prescription Drug User Fee Act action date of 23 August 2024.

The sBLA is based on results from Part 1 of the RUBY phase III trial. The trial met its primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS), demonstrating a statistically significant and clinically meaningful benefit in the overall population of patients treated with dostarlimab plus carboplatin-paclitaxel versus chemotherapy alone. RUBY Part 1 is the only clinical trial to show a statistically significant survival benefit in the overall patient population. The safety and tolerability analysis from RUBY showed a safety profile for dostarlimab and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents.

OS data were presented at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer on 16 March 2024.

About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries, with approximately 417,000 new cases reported each year worldwide1, and incidence rates are expected to rise by almost 40% between 2020 and 2040.2,3 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.4 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumours.5

About RUBY
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.

In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

About Jemperli (dostarlimab)
Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.6

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is dMMR, as determined by a US FDA-approved test, or MSI-H, and as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. The sBLA supporting this indication in combination with carboplatin and paclitaxel for dMMR/MSI-H primary advanced or recurrent endometrial cancer received Breakthrough Therapy designation and Priority Review from the US FDA. Jemperli is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli, and cobolimab (GSK4069889), a TIM-3 antagonist.

On April 24, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported that clinical data from the dose escalation portion of the Phase 1b/2 study of FG-3246 in combination with enzalutamide in patients with metastatic castration resistant prostate cancer have been selected for a poster presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 31-June 4, 2024 in Chicago, Illinois (Press release, FibroGen, APR 24, 2024, View Source [SID1234642279]).

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Details for the poster presentation are as follows:
Session: Poster Session – Genitourinary Cancer – Prostate, Testicular, and Penile
Title: A Phase 1b dose escalation study of FOR46, a novel antibody-drug conjugate targeting a tumor-specific epitope of CD46, in combination with enzalutamide (Enza) in patients with metastatic castration resistant prostate cancer (mCRPC).
Presenter: Nonna Shakhnazaryan and Dr. Rahul Aggarwal, MD from the UCSF Helen Diller Family Comprehensive Cancer Center
Abstract number: 5066
Poster number: 472
Date and Time: June 2, 2024 at 9:00-12:00 AM CDT

About FG-3246
FG-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 a tumor-specific 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 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 investigator-initiated Phase 1b/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 a Phase 2 monotherapy dose optimization study of FG-3246 in metastatic castration-resistant prostate cancer in 2H 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.

On April 24, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS) reported the first presentation of clinical data for CHS-114, a highly selective cytolytic anti-CCR8 antibody, at the upcoming ASCO (Free ASCO Whitepaper) Annual Meeting, which will be held from May 31 to June 4, 2024, at McCormick Place in Chicago (Press release, Coherus Biosciences, APR 24, 2024, View Source [SID1234642277]).

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Presentation Details

Abstract: 2664
Title: Preliminary Results of a Phase 1, First-in-human, Dose Escalation Study of the Anti-CCR8 Cytolytic Antibody, CHS-114 (formerly SRF114) in Patients with Advanced Solid Tumors.
Poster Session– Developmental Therapeutics – Immunotherapy
Date and Time: Saturday, June 1, 2024, 9:00 a.m. – 12:00 p.m. Central Daylight Time

About CHS-114

CHS-114, a human, afucosylated anti-CCR8 monoclonal antibody, is designed to selectively target human CCR8 and preferentially deplete CCR8+ regulatory T cells (Tregs) within the tumor microenvironment, not effector T (Teff) cells in tumors or Tregs in normal tissue. In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. In addition, treatment with CHS-114 alone reduced tumor growth in murine models, and enhanced antitumor activity was observed in combination with anti-PD-1 treatment.

CHS-114 is currently being evaluated in a Phase 1 clinical trial (NCT05635643) as a monotherapy and in combination with toripalimab in advanced solid tumors, including head and neck cancer. As reported in June 2023, early evidence of biological effect has been seen with CCR8+ Tregs depletion in blood following treatment with CHS-114, with no effect observed on non-CCR8+ Tregs. Clinical data from the CHS-114 single agent dose escalation stage of the Phase 1 study will be presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.

On April 24, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported its financial results for the first quarter of fiscal year 2024 (Press release, Chugai, APR 24, 2024, View Source [SID1234642276]).

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"Although revenue and profit decreased year on year due to the temporary impact of Ronapreve in the first quarter of 2024, the core business started off strong. In Japan, the sales of new products Phesgo and Vabysmo and a mainstay product Enspryng grew, but was notably impacted by the COVID-19 treatment Ronapreve, which its supply to the government has completed in the first quarter last year. As a result, domestic sales decreased by 46.4%. Overseas sales increased, with the substantial increase in exports of Hemlibra to Roche, despite the decrease in Actemra exports. In research and development, Piasky, our fifth global product, was approved in China and Japan. Currently, reviews for approval of the medicine are underway in other areas including the United States, Europe, and Taiwan. We aim to contribute to the treatment of paroxysmal nocturnal hemoglobinuria by providing a new option that improves convenience for patients affected by the disease, around the world. In addition, Alecensa was approved by the U.S. FDA for adjuvant treatment of ALK-positive non-small cell lung cancer. There are no other ALK inhibitors approved for this indication, bringing a new approach to patients. Regarding nemolizumab, another in-house project, development conducted by our out-licensing partners in Japan and overseas is making steady progress. In Japan, Mitchga as its product name was approved for the treatment of pruritus associated with atopic dermatitis in children aged 6 to 12 years, and for prurigo nodularis. Outside of Japan, the application was accepted by the U.S. and European authorities for the treatment of atopic dermatitis and prurigo nodularis. We will continue to drive forward the development of innovative medicines to provide new value to patients," said Dr. Osamu Okuda, Chugai’s President and CEO.

< First quarter results for 2024>

Chugai reported decreased revenue and operating profit year on year for the first quarter (Core-basis).

Regarding revenue, domestic sales decreased by 46.4% year on year. In the oncology field, although mature products such as Avastin were impacted by the NHI drug price revision and biosimilars, the overall decrease remained at 6.5% contributed by growth of new product Phesgo. In the specialty field, sales decreased by approximately 65%, mainly due to the completion of supply of Ronapreve to the government, which recorded ¥81.2 billion in the first quarter of last year, while our our new product Vabysmo grew and our mainstay product Enspryng performed well. Overseas sales increased year on year. Exports of Hemlibra increased by approximately 25%, exceeding the decrease in exports of Actemra. Other revenue increased substantially by approximately 60%, mainly driven by the increase in one-time income.

Cost to sales ratio improved by 16.3 percentage points year-on-year to 35.5%, mainly due to a change in the product mix. Research and development expenses increased mainly due to investments into drug discovery and early development, and increases associated with the progress of development projects. Selling, general and administration expenses remained at the same level as the previous year. Other operating income (expense) was ¥0.2 billion in income. As a result, Core operating profit totaled ¥102.1 billion (-3.1%).

Chugai also made good progress in research and development, in both early and late stages of developments, particularly in maximizing the value of in-house developed products and mainstay products. Regarding approvals, our fifth global product Piasky, a humanized anti-complement (C5) monoclonal antibody discovered by Chugai, has been approved for the first time in China for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), followed by approval in Japan. It is under review for PNH by other regulatory authorities, including in the United States, Europe, and Taiwan. Piasky is the second approved drug applying Chugai’s Recycling Antibody technology, following Enspryng. Another Chugai originated medicine, anti-IL-31RA, a humanized monoclonal antibody Mitchga (generic name: nemolizumab), has also been approved in Japan for additional indications including treatment for pruritus associated with atopic dermatitis (children aged ≥6 and <13 years) and prurigo nodularis (PN), only when existing treatment is insufficiently effective. Maruho, the out-license partner of nemolizumab in Japan has received these approvals. Additionally, Alecensa, which is also an in-house project, has been approved as an adjuvant therapy for ALK-positive non-small cell lung cancer, expanding its indication. As for projects in-licensed from Roche, Vabysmo, the only bispecific antibody in the ophthalmology field, has been approved for an additional indication for the treatment of macular edema associated with retinal vein occlusion. FoundationOne CDx Cancer Genomic Profile has been approved as companion diagnostics for three additional products, respectively.
Regarding filings, Chugai originated nemolizumab, developed by Galderma outside of Japan, has been accepted for review as a treatment for patients with PN and atopic dermatitis, by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). For PN, priority review designation has been granted by the U.S. FDA. As for projects in-licensed from Roche, the anti-CD20xCD3 bispecific antibody mosunetuzumab has been filed in Japan for the treatment of patients with relapsed or refractory follicular lymphoma. Furthermore, regulatory applications have been submitted for Evrysdi and Tecentriq for additional indications for pre-symptomatic spinal muscular atrophy and alveolar soft part sarcoma, respectively.
In addition, Chugai has in-licensed zilebesiran from Roche for the treatment of hypertension with high cardiovascular risk, and started a clinical study in Japan for RG6299, an antisense oligonucleotide targeting complement factor B, for the treatment of IgA nephropathy.

[2024 first quarter results]

Billion JPY 2024
Jan – Mar 2023
Jan – Mar % change
Core results
　Revenue 236.9 312.2 -24.1%
　　Sales 204.5 291.5 -29.8%
　　Other revenue 32.5 20.7 +57.0%
　Operating profit 102.1 105.4 -3.1%
　Net income 76.0 78.4 -3.1%
IFRS results
　Revenue 236.9 312.2 -24.1%
　Operating profit 99.9 98.3 +1.6%
　Net income 74.4 73.5 +1.2%
[Sales breakdown]

Billion JPY 2024
Jan – Mar 2023
Jan – Mar % change
Sales 204.5 291.5 -29.8%
　Domestic sales 103.2 192.7 -46.4%
　　Oncology 56.1 60.0 -6.5%
　　Specialty 47.0 132.7 -64.6%
　Overseas sales 101.3 98.8 +2.5%
[Oncology field (Domestic) Top5-selling medicines]

Billion JPY 2024
Jan – Mar 2023
Jan – Mar % change
　Tecentriq 14.5 15.1 -4.0%
　Avastin 8.7 13.0 -33.1%
　Polivy 7.4 7.2 +2.8%
　Alecensa 6.6 6.6 -
　Perjeta 6.1 7.5 -18.7%
[Specialty field (Domestic) Top5-selling medicines plus Ronapreve]

Billion JPY 2024
Jan – Mar 2023
Jan – Mar % change
　Hemlibra 12.5 12.4 +0.8%
　Actemra 10.2 9.9 +3.0%
　Enspryng 5.8 4.7 +23.4%
　Vabysmo 4.0 3.0 +33.3%
　Evrysdi 3.4 3.0 +13.3%
　Ronapreve* - 81.2 -100.0%
*Ronapreve has not been listed in the National Health Insurance (NHI) price list.

[Progress in R&D activities from Feb 2nd, 2024 to Apr 24th, 2024]

2024 Q1 R&D Progress
About Core results

Chugai discloses its results on a Core basis from 2013 in conjunction with its decision to apply IFRS. Core results are the results after adjusting non-Core items to IFRS results. Chugai’s recognition of non-recurring items may differ from that of Roche due to the difference in the scale of operations, the scope of business and other factors. Core results are used by Chugai as an internal performance indicator, for explaining the underlying business performance both internally and externally, and as the basis for payment-by-results such as a return to shareholders.

Trademarks used or mentioned in this release are protected by law.