On June 6, 2022 Thermo Fisher Scientific Inc., the world leader in serving science, and TransMIT GmbH Center for Mass Spectrometric Developments reported that spatial multi-omics applications in pharma and clinical labs (Press release, Lifescience Newswire, JUN 6, 2022, View Source [SID1234615684]).

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As part of the relationship, TransMIT will combine its proprietary scanning microprobe matrix-assisted laser desorption/ionization (SMALDI) MSI and 3D-surface MSI technology with the exceptional high resolution accurate mass (HRAM) power of Thermo Scientific Orbitrap MS instrumentation. TransMIT’s AP-SMALDI⁵ AF ion source coupled with Orbitrap MS technology enables spatial distribution mapping of a variety of molecules such as biomarkers, metabolites, peptides or enzymatically-digested proteins by their molecular masses. This approach can be applied to omics applications such as metabolomics, lipidomics, proteomics, glycomics and to pharmaco-kinetic studies in a variety of tissues.

"This co-marketing agreement will provide integrated solutions for mass spectrometry imaging, offering a label-free approach to map the distribution of a wide range of both known and unknown compounds directly sampled from biological tissue," said Jim Yano, senior director, life sciences mass spectrometry portfolio management, chromatography and mass spectrometry, Thermo Fisher Scientific. "Due to its high performance in spatial resolution, TransMIT’s AP-SMALDI⁵ AF ion source is the perfect match for the high mass resolution and accurate mass capabilities of the Orbitrap MS instrumentation."

Professor Bernhard Spengler, director, TransMIT Center for Mass Spectrometric Developments, said, "Our AP-SMALDI⁵ AF ion source coupled with Thermo Fisher’s Orbitrap technology create an MSI platform for high spatial resolution along with high mass resolution and mass accuracy. The AP-SMALDI-Orbitrap setup enables scanning of tissue samples or 3D objects with the pulsed laser beam of 5 μm spot size routinely without oversampling, providing a powerful solution for drug development and spatial multi-omics applications."

Announcement of the new co-marketing agreement coincides with the 70th American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics, being held June 5-9, 2022 where Thermo Fisher is showcasing its latest innovations in Booth 400 at the Minneapolis Convention Center, Minneapolis, Minnesota and at the Hilton Minneapolis Grand Ballrooms E, F, G.

On June 6, 2022 Elevar Therapeutics, Inc., a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, reported the results of its Phase 2 clinical trial (Study RM-202) of rivoceranib, an orally administered tyrosine kinase inhibitor (TKI), in patients with progressive recurrent or metastatic adenoid cystic carcinoma (R/M ACC) (Press release, Elevar Therapeutics, JUN 6, 2022, View Source [SID1234615682]).

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As shared in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, the results of Study RM-202 demonstrate the clinical effectiveness of rivoceranib for the treatment of patients with progressive R/M ACC, as indicated by substantially reduced tumor progression during the 6 months after rivoceranib treatment compared to that during the 6 months prior to rivoceranib treatment [-7.0 (-43 to 35) mm vs. 20.5 (5 to 180) mm].

The open-label study (NCT04119453) was conducted at 11 sites in the U.S. and South Korea to investigate the efficacy and safety of rivoceranib in patients with progressive R/M ACC. With 80 patients, including 53 (66.3%) based in the U.S., Study RM-202 is the largest to date involving a TKI in ACC patients.

All 80 participants demonstrated tumor progression within 6 months prior to the trial (by requirement). The study found an overall response rate (ORR) of 15.1% (a 30% reduction based on RECIST), and though not a study endpoint, the remaining 85% of patients had a reduction of tumor size.

"With every participant exhibiting a recent growing lesion upon entering this Phase 2 trial of rivoceranib, these results demonstrate significant clinical effectiveness and rivoceranib’s promise as a potential new treatment for patients with R/M ACC," said Saeho Chong, chief executive officer of Elevar. "Our entire Elevar team is greatly encouraged by these results, and we are fully focused on advancing rivoceranib through the regulatory process."

Other Study RM-202 key findings:

52% of patients had a response according to CHOI (size or density); CHOI is believed to be more correlated with median overall survival (mOS) than RECIST v1.1 (size only)
CHOI for Response: >10% reduction in tumor size or >15% reduction in tumor density
Median duration of response (mDoR) of 14.9 months
Median progression-free survival (mPFS) of 9 months versus published data of a baseline of 2.8 months for R/M ACC, and disease control for ≥ 3 months in over 60% of patients, regardless of prior vascular endothelial growth factor (VEGFR) therapy
Rivoceranib adverse event profile similar to other TKIs
"There is no approved standard of care for R/M ACC, so as we investigate rivoceranib’s potential as a treatment option we remain steadfastly focused on the many patients who now have or someday will be diagnosed with this disease," said Dr. Hyunseok Kang, medical oncologist at the University of California San Francisco and the primary investigator for Study RM-202. "The positive results demonstrated in this Phase 2 trial of rivoceranib represent a vitally important step forward for them."

Rivoceranib, which has been given orphan drug designation in the U.S., is a small molecule anti-angiogenic, with more than 6,000 patients studied in multiple cancers. Elevar has worldwide commercialization rights for rivoceranib, excluding China.

About ACC

Adenoid Cystic Carcinoma (ACC) is a rare malignancy that occurs within the secretory glands, most commonly in the major and minor salivary glands of the head and neck, but also found in the breast, skin and elsewhere. It is diagnosed in about 4 of every 1 million people each year – representing a combined 3,100 annual cases in the U.S., EU and Japan – and it afflicts more than 200,000 patients throughout the world, accounting for 5 percent to 7 percent of all head and neck malignancies, according to the Adenoid Cystic Carcinoma Research Foundation. There is no approved standard of care for R/M ACC patients. A previous study showed a baseline progression-free survival (PFS) of 2.8 months for ACC (Kang EJ, et al. Clin Cancer Res. 2021;27:5272-5279).

About Rivoceranib

Rivoceranib is the first small-molecule tyrosine kinase inhibitor (TKI) to be approved in gastric cancer in China (December 2014). Rivoceranib is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib, co-developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd. (JHP) in China and Elevar Therapeutics globally, with the exception of China. It has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy. Clinical studies are underway in multiple tumor types including gastric cancer (as a monotherapy and in combination with paclitaxel), hepatocellular carcinoma (combination with camrelizumab), adenoid cystic carcinoma and colorectal cancer (combination with Lonsurf). Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), adenoid cystic carcinoma (U.S.) and hepatocellular carcinoma (U.S.). Elevar holds the global rights (excluding China) and has partnered for the development and marketing of rivoceranib with HLB-LS in South Korea. Apatinib is currently approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, JHP, under the brand name Aitan.

On Jun. 6, 2022 Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) reported the closing of its previously announced underwritten public offering of 10,000,000 shares of its common stock to the public at $4.75 per share (Press release, Concert Pharmaceuticals, JUN 6, 2022, View Source [SID1234615681]). The aggregate gross proceeds to Concert from this offering were $47.5 million, before deducting underwriting discounts and commissions and other offering expenses payable by Concert. Concert also announced the receipt of $18.9 million upon the exercise of tranche 1 warrants to purchase 3,981 shares of Series X1 Preferred Stock issued to BVF Partners L.P. and RA Capital Management in November 2021. Through the public offering and warrant exercise, Concert raised aggregate gross proceeds of $66.4 million.

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Jefferies and Truist Securities acted as joint book-running managers for the offering. JMP Securities, A Citizens Company, and Mizuho Securities acted as lead managers, and H.C. Wainwright & Co. acted as co-manager for the offering.

The offering was made only by means of a written prospectus supplement and prospectus forming part of a shelf registration statement previously filed with the Securities and Exchange Commission (SEC) and declared effective on November 16, 2020. The final prospectus supplement and accompanying prospectus relating to the offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus may also be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected] or Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or other 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 other jurisdiction.

On June 6, 2022 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, and Pfizer Inc. (NYSE: PFE) reported that the National Medical Products Administration (NMPA) of China has approved sugemalimab (Cejemly) for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy (Press release, CStone Pharmaceauticals, JUN 6, 2022, View Source [SID1234615680]). Together with the previous approval of the treatment for first-line stage IV NSCLC patients, sugemalimab is now the only anti- PD-1/PD-L1 monoclonal antibody for both stage III and stage IV NSCLC patients.

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Dr. Frank Jiang, CEO of CStone, said, "We appreciate the NMPA for granting the new approval which is an important milestone in our journey to lead the treatment of lung cancer as China steps up efforts to support innovative therapies and address unmet needs. As a leading biopharma company in fostering precision medicines and immuno-oncology therapies, CStone has been spearheading multiple medical breakthroughs. With this approval, it will provide a new treatment option for stage III NSCLC patients, while demonstrating our prowess in advancing lung cancer treatments and bringing forward transformative drugs to the market. Partnerships are crucial to meet massive clinical needs of cancer patients. We will continue to work closely with Pfizer to deliver cutting-edge oncology therapies and improve the health of cancer patients in China."

Jean-Christophe Pointeau, China President of Pfizer Biopharmaceutical Group, says, "Committed to delivering ‘breakthroughs that change patients’ lives’, Pfizer has achieved a series of important breakthroughs in the field of immuno-oncology. After the approval of Stage IV NSCLC indication a few months ago, Cejemly achieved immediate commercialization across China, offering hopes to Chinese NSCLC patients with improved diagnosis and treatment solutions. We firmly believe that the approval of the new indication will allow more patients to benefit from this drug, bridge the gap and fulfill the unmet needs, especially the needs of unresectable Stage III NSCLC patients for immune consolidation therapy after sequential chemoradiotherapy. Cejemly is Pfizer’s strategic asset in immuno-oncology, and a paradigm for innovative strategic partnership with local biotech companies, like CStone guided by the slogan of "Science Will Win, Conquer Cancer Together". Starting from here, Pfizer will continue the exploration in this field, promote the upgrades and advances in immunodiagnostics and immunotherapy, offer more tailor-made, globally innovative solutions to Chinese cancer patients, and help to achieve the grand goal of "Healthy China 2030".

Professor Yi-Long Wu of Guangdong Provincial People’s Hospital, the Leading Principal Investigator on the GEMSTONE-301 study, said, "Patients with stage III NSCLC urgently need new treatment options, and the NMPA approval of sugemalimab brings them hope. The results from GEMSTONE-301 demonstrated that sugemalimab as a consolidation therapy had robust efficacy and a well-tolerated safety profile. It is now recommended by the Chinese Society of Clinical Oncology (CSCO) guidelines for this patient population. With proven clinical benefits, sugemalimab will potentially reshape the treatment landscape as a preferred immuno-oncology therapy for patients with mid- and late-stage lung cancer."

Dr. Jason Yang, Chief Medical Officer of CStone, said, "We are thrilled that sugemalimab has become the first anti- PD-1/PD-L1 monoclonal antibody approved for stage III NSCLC after concurrent or sequential chemoradiotherapy. The GEMSTONE-301 study has an innovative study design that enrolled patients with either concurrent or sequential chemoradiotherapy to better reflect real-world clinical practice and cover a broad patient population. We’ve also made significant progress in the registrational studies of sugemalimab in patients with esophageal squamous cell carcinoma, gastric cancer, and relapsed or refractory extranodal natural killer/T-cell lymphoma in a bid to benefit more cancer patients."

The NMPA approval is based on the GEMSTONE-301 study, a multicenter, randomized, double-blind phase 3 clinical trial, designed to evaluate the efficacy and safety of sugemalimab as a consolidation therapy in patients with unresectable stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy. Sugemalimab significantly improved patients’ progression-free survival (PFS). The risk of disease progression or death was reduced by 36%, together with encouraging overall survival (OS). Subgroup analyses demonstrated clinical benefits regardless of whether patients received prior concurrent or sequential chemoradiotherapy. Sugemalimab had a well-tolerated safety profile, and no new safety signals were observed. The results of the GEMSTONE-301 study were published in The Lancet Oncology in January 2022.

About Sugemalimab

The anti-PD-L1 monoclonal antibody sugemalimab was discovered by CStone using OmniRat transgenic animal platform, which allows creation of fully human antibodies in one step. Sugemalimab is a fully human, full-length anti-PD-L1 immunoglobulin G4 (IgG4) monoclonal antibody, which may allow a reduced risk of immunogenicity and toxicity for patients, a unique advantage over similar drugs.

Currently, the NMPA of China has approved sugemalimab (Cejemly) in combination with pemetrexed and carboplatin as first-line treatment of patients with metastatic non-squamous NSCLC, lacking epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genomic tumor aberrations; and in combination with paclitaxel and carboplatin as first-line treatment of patients with metastatic squamous NSCLC; for the treatment of patients with unresectable stage III NSCLC whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy.

With its proven therapeutic advantages, sugemalimab is set to be recommended by the 2022 CSCO clinical guidelines for the diagnosis and treatment of NSCLC, in combination with chemotherapy as the first-line treatment of patients with stage IV non-squamous/squamous NSCLC without driver alterations; or as a consolidation therapy in patients with stage III NSCLC after concurrent or sequential chemoradiotherapy.

CStone formed a strategic collaboration agreement with Pfizer that includes the development and commercialization of sugemalimab in mainland China, and a framework to bring additional Oncology medicines to the Greater China market.

On June 6, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported that proof-of-concept immune response data and first clinical data from its Phase 1/2 clinical trial of EO2401 in combination with an immune checkpoint inhibitor (nivolumab, Opdivo) in patients with non-resectable adrenocortical carcinomas (ACC), treated with at least one line (but not more than two prior lines of systemic therapy), or without prior systemic therapy for advanced/metastatic disease (SPENCER trial, EOADR1-19, NCT04116658) (Press release, Enterome, JUN 6, 2022, View Source [SID1234615679]). The data1 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, on June 4, 2022 in Chicago and virtually.

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EO2401 is Enterome’s first-in-class off-the-shelf OncoMimics cancer immunotherapy. It combines three OncoMimics peptides that closely mimic IL13Ra2, BIRC5 and FOXM1, all of which are known driver antigens present on aggressive solid tumors. In addition, EO2401 contains a CD4 helper peptide UCP2. Enterome selected these OncoMimics peptides using its Mimicry platform, which applies best-in-class biocomputational tools and bioassays to identify novel therapeutics from its proprietary database of 20+ million bioactive gut microbiome peptides and proteins.

Key highlights from the EO2401 poster presentation covering the Phase 1/2 SPENCER trial were:

Proof-of-concept immune response data

Immune monitoring of Cohort 2a demonstrates the ability of microbiome-derived peptides to induce a strong Tc1- skewed CD8+ T cell response with strong cross-reactivity against human selected tumor associated antigens.

The level of the specific CD8+ T cell immune responses against the microbiome-derived peptides comprising EO2401 were also found to correlate with clinical outcome (objective responses and progression-free survival).

Promising clinical outcome in sub-group of patients

The combination of EO2401 plus nivolumab was evaluated:

in patients with previously treated ACC (Cohort 2a, n=26) and
in patients who received no prior systemic therapy for advanced/metastatic disease (Cohort 2b, n=7)
Cohort 2a – group of patients showing benefit in objective tumor responses and time to progression

Analysis of Cohort 2a identified patients with clearly different efficacy outcomes, with one group showing benefit in objective tumor responses and time to progression, and another group with short progression-free survival (PFS) and short survival.

To refine the population for expansion in a randomized Phase 2 trial, different laboratory and clinical parameters were investigated as possible selection criteria.

No correlation was found between clinical outcome and tumor mutational burden, MSI-status, PD-L1 expression, serum cytokines/chemokines, or hormonal levels. However, the study found that patients in Cohort 2a who fulfilled the criteria of having received prior mitotane treatment, ECOG ≤ 1, ACC primary diagnosis > 9 months, max lesion size ≤ 125 mm, ≤ 3 organs involved, reduced lymphocytes ≤ grade 1 (n=14), demonstrated a clinical benefit vs patients not fulfilling these criteria (n=12), as follows:

Objective response rates (ORR) – 28.6% (95% CI 8.4; 58.1) vs 0% (95% CI 0.0; 26.5)
Disease control rates (DCR) – 64.3% (95% CI 35.1; 87.8) vs 8.3% (95% CI 0.2; 38.5)
Median progression-fee survival (PFS) – 3.9 months (95% CI 1.9; 9.2) vs 1.6 months (95% CI 0.5; 1.9)
Median survival – 13.0 months (95% CI 11.3; not evaluated) vs 2.1 months (95% CI 1.5; 7.4)
Cohort 2b – further follow up to be conducted

The clinical responses to EO2401 plus nivolumab observed in patients in Cohort 2b showed no benefit over the results from all patients in Cohort 2a, and further follow-up will be conducted.

Safety

The combination of EO2401, administered sub-cutaneously with the adjuvant Montanide ISA 51 VG, with nivolumab was well tolerated. The safety profile was consistent with the profile of nivolumab monotherapy, except the addition of local administration site reactions (occurring in 21% of patients).

Dr. Eric Baudin, Associate Professor and Head of the Endocrine Oncology Unit at the Institut Gustave Roussy (Villejuif, France) commented, "There has been no significant innovation in the treatment of advanced adrenal tumors and patients with this rare group of diseases are desperately in need of new effective therapies especially at relapse after first-line therapy. If confirmed, EO2401 in combination with nivolumab, represents the most promising therapy of the last three decades in this ultra rare cancer. I am pleased to be participating in this trial and to move forward into a randomized Phase 2 trial in this underserved patient population."

Dr. Jan Fagerberg, Chief Medical Officer of Enterome, said, "The data presented at ASCO (Free ASCO Whitepaper) for EO2401 in combination with nivolumab are very encouraging, with strong immune responses correlating to clinical outcome in patients having been previously treated for adrenocortical carcinoma. We are also pleased to have been able to define a set of clinical selection criteria that will enable us to refine a patient population for expansion in a Phase 2 randomized trial. We are on track to start this new trial in the coming months and look forward to the results in due course."

EO2401 in recurrent glioblastoma

At ASCO (Free ASCO Whitepaper), and separately announced today, Enterome presented the first clinical data from its Phase 1/2 clinical trials of EO2401 in combination with nivolumab +/- bevacizumab for the treatment of patients with recurrent glioblastoma (the ROSALIE trial, EOGMB1-18). View press release here.

About SPENCER

The SPENCER trial (EOADR1-19, NCT04187404) is a multicenter, open-label, Phase 1/2 study assessing the safety, tolerability, immunogenicity and preliminary efficacy of EO2401 in combination with the immune checkpoint inhibitor nivolumab in patients with adrenal tumors (adrenocortical carcinoma [ACC] and metastatic pheochromocytoma/paraganglioma [MPP]). The trial is expected to enrol at least 100 patients at clinical sites in Europe and the US.

References

Baudin, E. et al. EO2401, a novel microbiome-derived therapeutic vaccine for patients with adrenocortical carcinoma (ACC): Preliminary results of the SPENCER study. J Clin Oncol 40, 2022 (suppl 16; abstr 4596) doi: 10.1200/JCO.2022.40.16_suppl.4596