On June 1, 2023 Imugene Limited (ASX:IMU), a clinical stage immuno-oncology company, reported the first patient dosed in the combination cohort of the IMPRINTER study, a clinical trial to evaluate the safety and efficacy of Imugene’s PD1- Vaxx, a B-cell activating immunotherapy alone or in combination with atezolizumab (Tecentriq), an immune checkpoint inhibitor targeting PD-L1 from Roche, in patients with non-small cell lung cancer (NSCLC) (Press release, Imugene, JUN 1, 2023, View Source [SID1234632299]).

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The objectives of the open label, multi-center, dose escalation/expansion, phase 1/1b study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy as monotherapy or in combination with atezolizumab with or without chemotherapy, in adults with non-small cell lung cancer (IMPRINTER), are to determine safety, efficacy, and optimal dose of PD1-Vaxx in combination with atezolizumab as therapy in ICI treatment-naïve NSCLC patients or ICI pretreated patients. The study will be conducted at sites in USA and Australia.

Dual targeting of the PD-1/PD-L1 axis is an area of considerable interest, providing treatment options for patients with cancer. Combination with PD1-Vaxx may overcome treatment resistance to ICIs with dual inhibition of the PD-1/PD-L1 axis extending the treatment benefit of atezolizumab. In contrast to the combination of two monoclonal antibodies, PD1-Vaxx induces a unique polyclonal immune response which may increase response rates for the combination therapy.

Tecentriq has previously shown clinically meaningful benefit in various types of lung cancer, with six currently approved indications in the US. In addition to becoming the first approved cancer immunotherapy for adjuvant NSCLC, Tecentriq was also the first approved cancer immunotherapy for front-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy). Tecentriq also has four approved indications in advanced NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies.

Imugene MD & CEO Leslie Chong said "It’s an outstanding accomplishment to see Imugene collaborate with Roche, in combination with our PD1-Vaxx drug. PD1-Vaxx has shown a tolerable safety profile and encouraging efficacy in patients with NSCLC, and with the first patient being dosed today, we are looking forward to evaluating PD1-Vaxx with atezolizumab in ICI treatment- naïve and pre-treated NSCLC patients."

Imugene is the sponsor of the study and is funding the clinical study from existing budgets and resources. Roche will provide atezolizumab for the duration of the study. There are no preconditions to this supply agreement. The supply agreement is for a period of up to five years unless agreed otherwise by either party with industry standard cancellation provisions including termination without penalty. All data generated in the performance of the study in accordance with the supply agreement shall be the property of Imugene as
the sponsor of the study. All rights to all inventions and discoveries made or conceived in the course of the study relating to the combination of atezolizumab and PD1-Vaxx shall belong jointly to Roche and Imugene.

On June 1, 2023 AstraZeneca and MSD’s reported that Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone has been approved in the US for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC) (Press release, AstraZeneca, JUN 1, 2023, View Source [SID1234632295]).

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This approval was based on a subgroup analysis of the Phase III PROpel trial which showed that Lynparza plus abiraterone demonstrated highly clinically meaningful improvements in both radiographic progression-free survival (rPFS) (HR of 0.24, 95% CI, 0.12-0.45) and overall survival (OS) (HR of 0.30, 95% CI, 0.15-0.59) versus abiraterone alone in patients with BRCA mutations.1 Median rPFS and median OS were not reached for patients treated with Lynparza plus abiraterone versus a median of 8 months and 23 months, respectively, for those treated with abiraterone alone.

Prostate cancer is the second-most common cancer in men and despite an increase in the number of available therapies for patients with mCRPC, five-year survival remains low.2,3 Approximately 10% of patients with mCRPC have BRCA mutations, which is associated with poor prognosis and outcomes.4,5

Andrew Armstrong, MD, ScM, of the Duke Cancer Institute, Durham, North Carolina, US, and an investigator in the trial, said: "Preventing or delaying radiographic progression or death is an important clinical endpoint in assessing cancer treatment and is very important to patients, their caregivers and their families. The PROpel results showed the Lynparza combination demonstrated a notable clinically meaningful benefit that should rapidly be considered as the standard of care treatment for patients with BRCA-mutated metastatic castration-resistant prostate cancer."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "There is a critical unmet need for new first-line treatment options for patients with BRCA-mutated metastatic castration-resistant prostate cancer and this approval underscores the importance of BRCA testing at metastatic diagnosis. We look forward to bringing the benefit of this Lynparza combination to patients earlier in their treatment."

Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: "It is imperative that we create new ways to treat advanced cancers and help improve patient outcomes by building on the current standard of care. In PROpel, the Lynparza combination improved radiographic progression-free survival and overall survival for the subgroup of patients with BRCA-mutated metastatic castration-resistant prostate cancer. This approval reinforces the importance of routine testing for genetic mutations at metastatic diagnosis to help guide clinical decisions."

The safety and tolerability profile of Lynparza plus abiraterone in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines.

Lynparza in combination with abiraterone and prednisone or prednisolone is approved in the European Union (EU) and several other countries for the treatment of adult patients with mCRPC based on the PROpel trial.

Lynparza is already approved in the US based on results from the PROfound Phase III trial as monotherapy for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCAm and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan, and China for patients with BRCAm mCRPC who have progressed following prior therapy that included a new hormonal agent.

Financial considerations
Following this approval for Lynparza in the US, AstraZeneca will receive a regulatory milestone payment from MSD, anticipated to be booked as Collaboration Revenue by the Company and confirmed in the second quarter 2023 results.

Notes

Prostate cancer
Prostate cancer is the second most commonly diagnosed cancer in men and the fifth leading cause of cancer death in men globally, with an incidence of 1.4 million and 375,000 deaths in 2020.2,3 In the US, it is estimated that there will be 288,300 new cases and 34,700 deaths in 2023.6 Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real-world.7 Approximately half of patients with mCRPC may receive only one line of active treatment, and those that go on to receive further treatment often have diminishing benefit of subsequent therapies.8-13

Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.14 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.15

In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.16 Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.17 Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.17

Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent (NHA) treatment, there is high unmet need in this population.16-19

PROpel
PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of Lynparza versus placebo when given in combination with abiraterone, as well as prednisone or prednisolone, in men with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting.

The primary endpoint is rPFS and secondary endpoints include OS, time to secondary progression or death, and time to first subsequent therapy. In September 2021 at a planned interim analysis, the Independent Data Monitoring Committee concluded that the PROpel trial met the primary endpoint of rPFS.

For more information about the trial please visit ClinicalTrials.gov.

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in HRR, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.

Lynparza is currently approved in a number of countries across multiple tumour types including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated (EU) and as monotherapy in HRR gene-mutated metastatic castration-resistant prostate cancer in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan). In China, Lynparza is approved for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer, as a 1st-line maintenance therapy in BRCA-mutated advanced ovarian cancer as well as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 75,000 patients worldwide. Lynparza has a broad clinical trial development programme, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

On June 1, 2023 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported that it has expanded the clinical collaboration and supply agreement with Roche to cover evaluation of VB10.16, Nykode’s wholly owned off-the-shelf therapeutic cancer vaccine candidate, in combination with Roche’s cancer immunotherapy atezolizumab in patients with advanced cervical cancer who have progressed on pembrolizumab plus chemotherapy +/-bevacizumab as first line treatment (Press release, Nykode Therapeutics, JUN 1, 2023, View Source [SID1234632286]). The VB-C-04 trial is expected to be initiated in the U.S. in the fourth quarter of 2023 with registrational intent, which provides a potential fast-to-market path.
Under the terms of the agreement, Nykode will sponsor and fund the planned clinical trial, and Roche will provide atezolizumab. Nykode retains all commercial rights to VB10.16 worldwide.

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Nykode has recently reported positive safety and efficacy results from the Phase 2 VB-C-02 trial in Europe in advanced cervical cancer patients with VB10.16 in combination with atezolizumab. The results showed an overall response rate (ORR) of 29%, median overall survival (mOS) not reached but greater than 25 months at the time of analysis, and 6.3 months median progression free survival (mPFS) in PD-L1+ patients. In the patient population most relevant for the upcoming VB-C-04 trial, PD-L1+ patients with one prior line of systemic treatment, ORR was 40% and disease control rate was 80% with mPFS of 16.9 months and mOS not reached but greater than 25 months at the time of analysis.

"We look forward to expanding our collaboration with Roche to bring the combination of VB10.16 and atezolizumab to cervical cancer patients with limited treatment options. Cervical cancer has a poor prognosis, and the recent positive clinical data from VB-C-02 has strengthened our commitment to contribute with a well-tolerated treatment that can potentially prolong the life of these women. The trial provides a potential fast path to market for VB10.16." said Michael Engsig, CEO of Nykode Therapeutics. "Overall, the collaboration speaks to our shared confidence in the unique potential of VB10.16, the platform, and the synergy between our vaccine candidates and atezolizumab.

In addition to the existing VB-C-02 and the new VB-C-04 collaboration, Roche continues to be a valuable partner under our collaboration agreement covering development of individualized vaccines for a broad range of cancers." The VB-C-04 trial will be conducted together with GOG Foundation, a U.S.-based not-for-profit organization with expertise in bringing best-in-class new treatments to patients.

About VB10.16

VB10.16 is a potentially first-in-class off-the-shelf therapeutic cancer vaccine candidate in development for the treatment of human papillomavirus type 16 (HPV16)-positive cancers. The cancer vaccine is designed based on Nykode’s Vaccibody technology platform of targeting antigens to antigen presenting cells. VB10.16 has reported positive data from a Phase 2 trial in advanced cervical cancer patients (NCT04405349) in combination with atezolizumab with mOS not reached but greater than 25 months at the time of analysis in PD-L1+ patients. The vaccine-induced significant HPV16-specific T cell responses were correlated with clinical responses. The candidate has also demonstrated favorable clinical data in a Phase 1/2a study in pre-cancerous HPV16-induced high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3) demonstrating a statistically significant correlation of immune responses and clinical responses.

About Cervical Cancer

Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed between the ages of 35 and 44. Each year around 600,000 women are diagnosed with cervical cancer worldwide. Almost all cases are caused by human papillomavirus (HPV) infection and HPV16 accounts for more than half of all cervical cancer cases. Approximately 80% of patients with cervical cancer have squamous cell carcinoma (arising from cells lining the bottom of the cervix) and most other patients have adenocarcinomas (arising from glandular cells in the upper cervix). Cervical cancer is often curable when detected early and effectively managed, but treatment options are more limited in advanced disease stages or when the cancer has spread.

On May 31, 2023 HOOKIPA Pharma Inc. (Nasdaq: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported the pricing of an underwritten public offering of 22,900,768 shares of its common stock and 15,268 shares of its non-voting Series A-2 convertible preferred stock (the "Offering") (Press release, Hookipa Pharma, JUN 1, 2023, View Source [SID1234632274]). The public offering price of each share of common stock is $1.31 and the public offering price of each share of non-voting Series A-2 preferred stock is $1,310.00 (each share of non-voting Series A-2 preferred stock is convertible into 1,000 shares of common stock). The gross proceeds to HOOKIPA from this offering are expected to be approximately $50.0 million, before deducting underwriting discounts and commissions and other offering expenses. All of the securities in the Offering are to be sold by HOOKIPA. The Offering is expected to close on June 5, 2023, subject to customary closing conditions.

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SVB Securities and RBC Capital Markets are acting as joint book-running managers for the Offering. H.C. Wainwright & Co. and JMP Securities, a Citizens Company, are acting as lead managers for the Offering.

The securities described above are being offered by HOOKIPA pursuant to a shelf registration statement on Form S-3 (No. 333-266104), including a base prospectus filed with the Securities and Exchange Commission (the "SEC"), which was declared effective on July 21, 2022. A final prospectus supplement and accompanying prospectus relating to the Offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained, when available, from SVB Securities LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston Massachusetts 02109, by telephone at 1-800-808-7525 ext. 6105, or by email at [email protected]; RBC Capital Markets, LLC, Attention: Equity Capital Markets, 200 Vesey Street, 8th Floor, New York, NY 10281, by telephone at 877-822-4089, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.