Innovent and Laekna Jointly Announce First Patient Dosed with Three-drug Combination in a Phase 1/2 Study for the Treatment of Patients with Solid Tumors Who Were Resistant to Prior Anti-PD-1/PD-L1 Therapy

On July 31, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, autoimmune, metabolic, ophthalmology and other major diseases, and Laekna Therapeutics, a clinical-stage biotechnology company dedicated to bringing ground-breaking therapies to cancer and liver fibrosis patients worldwide, reported that the first patient has been dosed in a Phase 1/2 clinical trial (clinicaltrials.gov, NCT05383482) of a three-drug combination therapy (afuresertib + sintilimab + chemotherapy) in patients with specific solid tumors who were resistant to anti-PD-1/PD-L1 therapy at the West China Second Hospital of Sichuan University (Press release, Innovent Biologics, JUL 31, 2022, View Source [SID1234617158]). This marks a key milestone on the first anniversary of the clinical research partnership established between Innovent and Laekna in July 2021.

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The study is a multi-center, single-arm, open-label, dose-escalation Phase 1/2 clinical study, assessing recommended Phase 2 dose (RP2D), safety, tolerability and anti-tumor activity of afuresertib in combination with sintilimab and chemotherapy (nab-paclitaxel or docetaxel) in patients with solid tumors who were resistant to prior anti-PD-1/PD-L1 therapy. The principal investigator of the study is Professor Lin Shen, Director of the Department of Gastrointestinal Oncology of Beijing Cancer Hospital. The primary endpoints of the Phase 1 dose escalation study are maximum tolerated dose (MTD) and RP2D, and the primary endpoint of the Phase 2 study is overall response rate (ORR). The study is planned to be extended as a multi-regional clinical trial at the pivotal stage.

The clinical trial assesses five types of solid tumors, including non-small cell lung cancer (NSCLC), gastric cancer/gastroesophageal junction cancer (GC/GEJC), esophageal cancer (EsC), cervical cancer (CC) and endometrial cancer (EC). The study focuses on the AKT inhibitor, a potential new therapy for drug resistant-cancer, to address the unmet medical needs in cancer immunotherapy resistance and bring hope to solid tumor patients who have received prior anti-PD-1/PD-L1 treatments.

The combination therapy consists of Laekna’s afuresertib (LAE002), a highly selective ATP competitive AKT inhibitor in pivotal clinical trials with favorable clinical efficacy and safety profile, and Innovent’s PD-1 inhibitor sintilimab (TYVYT), which has been approved for six indications in China with the first four included in the National Reimbursement Drug List (NRDL).

The subject who received the first dose was a patient with cervical cancer. Professor Rutie Yin, investigator of the center where the first patient was dosed and Director of the Department of Chemoradiotherapy Oncology at the West China Second Hospital of Sichuan University, said, "Cervical cancer is the fourth most common cancer globally in women1. In 2020, China reported about 110,000 new cases and about 60,000 death cases of cervical cancer2. Patients are faced with limited treatment options and the prognosis is poor3,4. Immunotherapy plays an increasingly important role in the treatment of recurrent or metastatic cervical cancer, and there is huge unmet need. With the launch of new immunosuppressants, they’ve been applied to more patients and become essential for the treatment of cervical cancer. AKT inhibitor, a serine/threonine-specific protein kinase, is considered a potential new target for cancer treatment as results of multiple preclinical studies showed that inhibition of AKT could restore the sensitivity of cancer cells to anti-tumor therapies. We look forward to the progress of the clinical trial and hope it will bring new breakthroughs to the later-line treatment of cervical cancer in China."

Professor Lin Shen, principal investigator of the study, Director of the Department of Gastrointestinal Oncology of from Beijing Cancer Hospital, stated, "Innovation never stops in oncology as we are always looking for new ways to treat cancer patients. Based on results from the preclinical and clinical studies, the combination of an immune checkpoint inhibitor, an AKT inhibitor and taxanes shows potential to be a new treatment option for patients who were resistant to immune checkpoint inhibitors5,6,7,8. The trial conducted by Laekna and Innovent aims to explore this innovative combination therapy and validate this new promising solution. There is a significant clinical need for patients with digestive system and gynecologic solid tumors in China; we hope to see that AKT-targeting therapy will prove to be an effective strategy to overcome drug resistance."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "With the increasing prescription of immune checkpoint inhibitors (ICI) in first-line settings in various tumor types, many patients developed ICI resistance or have poor response rates in clinical practice. It is of great clinical value to explore potential treatments for this huge unmet medical need. Sintilimab is the first PD-1 inhibitor in China with first-line indications for 5 major types of cancers. Innovent hopes to continue to develop the potential of high-quality drugs, in this case by combination therapy with Laekna’s innovative AKT inhibitor. We look forward to the results of clinical trial to bring clinical benefits to patients with specific solid tumors."

Dr. Yong Yue, Chief Medical Officer of Laekna, said, "It took less than six months to complete the journey from IND approval to dosing of first patient, showing robust strategic execution of Laekna’s global clinical team. There are three main considerations in selecting the five types of solid tumors: PD-1/PD-L1 inhibitors have been approved as the standard-of-care treatments for those cancers in multiple countries; higher rates of biomarkers that activate the AKT pathway in patients with resistance to anti-PD-1/PD-L1 therapy were observed in those cancers; and the incidence rates and death rates are relatively high in China. We hope this innovative three-drug combination therapy will benefit patients with these solid tumors."

About Afuresertib (LAE002)

Afuresertib (LAE002) is an investigational highly selective adenosine triphosphate (ATP) competitive AKT inhibitor.

Laekna in-licensed afuresertib from Novartis in 2018 and are conducting five combination therapy clinical trials for the treatment of ovarian cancer, prostate cancer, breast cancer, and PD-1/PD-L1-resistant solid tumors. Prior to Laekna’s in-licensing agreement, over 10 clinical trials had been conducted to demonstrate the safety and efficacy profiles of afuresertib. In the Phase Ib study conducted by Novartis, afuresertib showed potential anti-tumor efficacy in platinum-resistant ovarian cancer (PROC) patients with an overall response rate (ORR) of 32.1% and progression-free survival (PFS) of 7.1 months9. In pre-clinical studies, afuresertib has demonstrated its ability to restore platinum/paclitaxel sensitivity in PROC cell lines. After the in-licensing agreement, Laekna also identified the therapeutic potential of combining afuresertib and LAE001 (an investigational potential first-in-class next-generation androgen synthesis inhibitor that simultaneously inhibits both CYP17A1 and CYP11B2) and observed their synergistic anti-tumor efficacy in our completed Phase 1 and ongoing Phase 2 studies in metastatic castration-resistant prostate cancer (mCRPC) patients as second- to fourth-line treatments. According to Frost & Sullivan, afuresertib is one of the three AKT inhibitors worldwide that have entered pivotal clinical trials10.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody jointly developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells11. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for six indications as below, with the first four included in the National Reimbursement Drug List (NRDL), including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of non-squamous non-small cell lung cancer lacking EGFR or ALK driver mutations;
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer;
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of unresectable or advanced hepatocellular carcinoma;
In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
In combination with fluorouracil and platinum-based chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Innovent currently has the regulatory submission for sintilimab in combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment under review in the China’s NMPA.

Additionally, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

EpiAxis highlights – July 2022

On July 30, 2022 EpiAxis Therapeutics reported to update venture capitalists, corporate investors, private investors and investment bankers on its latest epigenetic findings (Press release, EpiAxis Therapeutics, JUL 30, 2022, View Source;utm_medium=rss&utm_campaign=epiaxis-highlights-july-2022 [SID1234617155]).

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The company is currently working with The Sage Group to raise US$12million to advance a candidate into an IND enabled program following the findings of its pioneering clinical trial EPI-PRIMED. This was the first time that an epigenetic inhibitor had been used in combination with chemotherapy to treat metastatic breast cancer and the findings give EpiAxis a solid foundation for its next clinical trial using its novel peptide inhibitors..

EpiAxis CEO Dr Jeremy Chrisp pitched at youngStartup Ventures Network’s Venture Summit West 2022, which was held in Silicon Valley from 19-20 July 2022.

The exclusive venture summit focused on emerging and early stage companies as well as showcasing more than 100 top innovators in the tech, fintech, cleantech, lifesciences, healthcare and medtech sectors.

Venture Summit West only accepts presenters who meet strict criteria based on industry, stage, business model, size of the target audience, milestones achieved to date, and whether the company would be of interest to the featured investors. Its presentation programs are geared toward emerging growth companies looking to gain visibility among active investors and raise capital.

"We were excited to be one of only 200 companies worldwide to earn a coveted presentation spot at the 10th annual Venture Summit West," said Dr Chrisp. "It was energising to increase investor awareness in the advances that have been made in epigenetic treatments for metastatic cancer."

Wholesale Investor also shared the results of EpiAxis’ EPI-PRIMED trial with its engaged and growing ecosystem of over 29,300 high-net-worth investors, fund managers, family offices, PE and VC firms, government bodies and industry participants.

Wholesale Investor is Australasia’s leading investment platform. It connects innovative, emerging companies that are looking to raise capital with its active investor base.

Summary of Consolidated Financial Results [Japanese GAAP] For the First Quarter of the Fiscal Year Ending March 31, 2023

On July 29, 2022 Nippon Kayaku reported that (Press release, Nippon Kayaku, JUL 29, 2022, View Source [SID1234617328])

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1. Consolidated Business Results for the First Quarter of Fiscal Year Ending March 31, 2023 (April 1, 2022– June 30, 2022) (Figures shown are rounded down to the nearest million yen.)
(1) Consolidated Operating Results
(2) Consolidated Financial Position

2. Status of Dividends

3. Consolidated Business Results Forecasts for the Fiscal Year Ending March 31, 2023 (April 1, 2022– March 31, 2023)

1. Qualitative Information Concerning Results for the First Quarter
(1) Analysis of Operating Results During the first quarter of this consolidated fiscal year (April 1 to June 30, 2022), the global economy saw a return to normalcy from the COVID-19 pandemic, mainly in Europe and the U.S. However, the sense of uncertainty increased even more as a result of the zero COVID policy in China, the Russian invasion of Ukraine, and increasing global inflation caused by high fuel and raw material prices.

The Nippon Kayaku Group launched KAYAKU Vision 2025, the new mid-term business plan beginning this fiscal year, amid such conditions. We are working to implement the roadmap to the vision specified for each business while advancing initiatives to address key company-wide issues aimed at achieving the vision. As a result, net sales for the first quarter of this consolidated fiscal year totaled 48,296 million yen, an increase of 1,849 million yen (4.0%) year-on-year. Sales in the pharmaceuticals and other businesses underperformed while the functional chemicals and safety systems businesses outperformed the first quarter of the previous fiscal year. Operating income totaled 6,380 million yen, an increase of 493 million yen (8.4%) year-on-year. Ordinary income totaled 8,634 million yen, an increase of 2,285 million yen (36.0%) year-on-year.

Profit attributable to owners of parent was 5,957 million yen, an increase of 691 million yen (13.1%) year-on-year. The figures in the provisional accounting for a business combination in the second quarter of the previous consolidated fiscal year have been confirmed. The content confirmed in the provisional accounting is reflected in the figures for the first quarter of the previous consolidated fiscal yearPerformance by business segment is as described below. [Functional Chemicals Business] Sales rose to 21,117 million yen, an increase of 1,027 million yen (5.1%) year-on-year. The functional materials business as a whole outperformed the first quarter of the previous fiscal year. The outperformance resulted from strong sales of semiconductor materials such as epoxy resins, MEMS, and other resin composites.

These materials are used in high-speed (5G) communication devices and IoT, which are proliferating, and IT equipment, where demand increased due to increasingly sophisticated electronic equipment in vehicles. The color materials business as a whole outperformed the first quarter of the previous fiscal year. This outperformance resulted from strong sales of colorants for inkjet printers for consumer use, which more than compensated for the underperformance of colorants for inkjet printers in industrial applications compared to the first quarter of the previous fiscal year. The catalyst business underperformed the first quarter of the previous fiscal year despite strong orders both in Japan and exports overseas. The underperformance resulted from delays in freight reaching customer plants due to the lock-downs and logistics chaos that accompanied China’s zero COVID policy. In the Polatechno business, demand for dye-type polarizing films declined due to a shortage of semiconductors at customer plants.

This decline exceeded the strong sales of components for X-ray analysis systems and resulted in underperformance of the Polatechno business as a whole, compared with the first quarter of the previous fiscal year. Segment profit totaled 3,760 million yen, an increase of 361 million yen (10.6%) year-on-year. This increase resulted from growth in sales in the functional materials and color materials businesses.

Entry into a Material Definitive Agreement

On July 29, 2022, Vericel Corporation (the "Company"), as borrower, reported that entered into a $150 million five-year senior secured revolving credit facility ("the Facility") pursuant to a Senior Secured Revolving Credit Agreement by and among the Company, the lenders party thereto, and J.P. Morgan Chase Bank, N.A., as the administrative agent (the "Revolving Credit Agreement") (Filing, 8-K, Vericel, JUL 29, 2022, View Source [SID1234617283]). J.P. Morgan Chase Bank, N.A. also acted as sole bookrunner and sole lead arranger under the Revolving Credit Agreement.

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Proceeds of the Facility may be used for general corporate purposes, including, without limitation, acquisitions and capital expenditures, and such other uses as permitted under the Revolving Credit Agreement.

Except for certain excluded property as described in the Revolving Credit Agreement, the Facility is secured by a first priority lien on substantially all of the assets of the Company, and includes a $5,000,000 limit for swingline loans. In addition, the Facility includes a $15 million sub-facility for the issuance of letters of credit.

Outstanding borrowings under the Revolving Credit Agreement bear interest, with pricing based from time-to-time at the Company’s election at (i) SOFR plus 0.10% plus a spread ranging from 1.25% to 2.50% as determined by the Company’s total net leverage ratio (as defined in the Revolving Credit Agreement) or (ii) the alternative base rate (as defined in the Revolving Credit Agreement) plus a spread ranging from 0.25% to 1.50% as determined by the Company’s total net leverage ratio. The Revolving Credit Agreement also includes a commitment fee, which ranges from 0.20% to 0.25% as determined by the Company’s total net leverage ratio.

All commitments under the Revolving Credit Agreement shall terminate and the Facility will mature on July 29, 2027.

The Revolving Credit Agreement includes customary affirmative and negative covenants, including financial covenants requiring the Company to maintain a maximum total net leverage ratio, and certain limitations on the incurrence of additional indebtedness and liens, as well as usual and customary events of default for revolving credit facilities of this nature.

The foregoing summary of the Revolving Credit Agreement does not purport to be complete and is qualified in its entirety by reference to the agreement, which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending September 30, 2022.

Upsher-Smith Enters Into Exclusive Agreement with Emphascience for Development of Specialty Branded Generic Product

On July 29, 2022 Upsher-Smith Laboratories, LLC (Upsher-Smith) reported that it has entered into an exclusive agreement with Emphascience, Inc. (Emphascience) to support the development of a specialty branded generic product (Press release, Upsher-Smith Laboratories, JUL 29, 2022, View Source [SID1234617231]). This collaboration is part of Upsher-Smith’s company-wide effort to grow the Company’s portfolio of products through strategic partnerships and product acquisitions.

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Under the terms of the agreement, Emphascience will develop the product exclusively for Upsher-Smith. Upsher-Smith will manufacture, market and distribute it under its own label in the U.S. upon FDA approval. Financial terms related to the deal have not been disclosed.

"Upsher-Smith is committed to growing its ANDA portfolio through external programs and strategic partnerships that will drive volume to our new manufacturing facility," said Rich Fisher, President and COO, Upsher-Smith. "We look forward to working with Emphascience, a company that is well known for its development expertise as we continue to expand our portfolio with high-touch generic products that could fill unmet patient needs."

Rebanta Bandyopadhyay, Ph.D., President and CEO of Emphascience added, "We are excited to partner with such a well-regarded, trusted, quality-conscious, and patient-focused pharmaceutical company as Upsher-Smith Laboratories, to apply our technical skills and scientific acumen in designing and developing high quality, innovative medicines that truly impact patients’ lives."

Upsher-Smith will open its world-class manufacturing facility in Maple Grove, MN later this year. The new, 270,000 square foot facility will have fully up-to-date serialization and packaging capabilities and has capacity and capabilities that can support contract manufacturing for third parties. To learn more, visit www.upsher-smith.com.