On July 26, 2021 CRCbioscreen, a Dutch diagnostics company, reported to developing a next generation stool test for population based ColoRectal Cancer or CRC screening, reported the publication of promising results of a diagnostic accuracy study with a multitarget immunochemical test (mtFIT) for early detection of CRC (Press release, CRC bioscreen, JUL 26, 2021, View Source [SID1234585204]). Data were published in the prestigious journal Annals of Internal Medicine. The researchers found that the combination of 3 biomarkers (hemoglobin, calprotectin and serpin F2) had significantly higher sensitivity compared with the standard FIT test, without compromising specificity. The mtFIT detects 35% more advanced adenomas, which could translate into 12% CRC incidence reduction and 8% CRC mortality reduction.

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The paper was authored by a team of researchers and clinicians from the Netherlands Cancer Institute, Amsterdam, in collaboration with researchers from AmsterdamUMC and ErasmusMC in Rotterdam, The Netherlands.

Addition of protein biomarkers

The researchers used bio-banked residual FIT sample buffer from 1,284 patients to assess if the addition of protein biomarker quantification in stool could be used to improve the sensitivity of FIT, without sacrificing specificity. The patients were classified by their most advanced lesion – CRC, advanced adenomas, advanced serrated polyps, nonadvanced adenomas, and nonadvanced serrated polyps—and then classification and regression tree (CART) analysis was applied to biomarker concentrations in order to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a ‘leave-one-out’ approach and compared with FIT at equal specificity.

Sensitivity increased by 35% for advanced adenomas

The researchers found that the combination of 3 biomarkers (hemoglobin, calprotectin and serpin F2) had significantly higher sensitivity than FIT for advanced neoplasia (i.e. CRC and advanced precursor lesions) with equal specificity to FIT. The improvement was seen in the advanced adenomas, for which sensitivity was increased by 35%, while sensitivity for CRC and advanced serrated polyps did not change. The improved sensitivity for advanced adenomas may prove critical to improving FIT’s performance as a cancer prevention test. The authors estimate that when performed biennially and compared to traditional biennial FIT, mtFIT would reduce CRC incidence and mortality by 12% and 8%, respectively, assuming 73% adherence.

Finally, the mtFIT was also deemed cost-effective. Funding has been secured to conduct a prospective screening trial to further validate mtFIT within the context of the Dutch CRC screening program.

An independent editorial comment in the same issue of the journal commented on the study to be "important because the challenge of building a better screening test was approached from the perspective of an organized, population-based screening program, and it shows the potential of relatively inexpensive enhancements to the widely used FIT to improve sensitivity without sacrificing specificity" and "Ultimately, this study offers promise of incremental but important improvements in the effectiveness of population-based CRC screening through novel biomarker measurement using an existing screening platform."

Prof. Dr. Gerrit Meijer, CRCbioscreen’s CSO and principal investigator, commented:

"We are very pleased with the results of this diagnostic accuracy study. There is a need for a noninvasive screening test that has higher sensitivity for precursor lesions without increasing false-positive test results. This multitarget protein-based test shows a substantial improvement over FIT in detecting advanced adenomas, while the test logistics still remain fully compatible with that of current FIT based population screening programs. Early detection of colorectal cancer can save many lives. These data underscore our commitment to contribute to a substantial worldwide reduction in incidence and deaths due to this life-threatening disease."

Dr. Meike de Wit, CRCbioscreen’s COO and corresponding author, adds:

"These findings provide a solid basis for conducting a prospective screening trial in the context of the Dutch national CRC screening program. In that study, which is co-funded by CRCbioscreen and is planned to be launched this autumn, the multitarget FIT will be compared to FIT in 13,000 participants of the Dutch national colorectal cancer screening program."

On July 26, 2021 Harbour BioMed ("HBM", HKEX: 02142) reported that the abstract detailing clinical data from its Australian phase I study of next-generation anti-CTLA-4 antibody in patients with advanced solid tumors will be presented as an e-poster at the 2021 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, which is expected to be held 16-21 September 2021 (Press release, Harbour BioMed, JUL 26, 2021, View Source [SID1234585203]).

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As the first fully human heavy chain only antibody (HCAb) under the clinical investigation, HBM4003 is generated from Harbour Mice platform. This Study is an open-label, dose-escalating monotherapy study in treatment of advanced solid tumors. The preliminary clinical data demonstrate encouraging anti-tumor efficacy of HBM4003 with the good safety profile and tolerability. The data obtained from the Study have further validated pre-clinical findings of HBM4003’s unique PK/PD profile, novel mechanism of action and low immunogenicity. The Company has proceeded with multiple global phase Ib/IIa trials in solid tumors in light of the encouraging clinical efficacy and safety profile.

About HBM4003

HBM4003 is the fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, HBM 4003 has demonstrated significantly improved depletion specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combo-therapy.

On July 26, 2021 Kiromic Biopharma, Inc. (Nasdaq: KRBP), a pioneer in immuno oncology cellular therapy in solid tumors, reported it has completed the acquisition of InSilico Solutions (Press release, Kiromic, JUL 26, 2021, View Source [SID1234585202]).

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InSilico Solutions is a world-class bio-informatics and artificial intelligence innovator with a long standing collaborative relationship with its clients at MD Anderson Cancer Center, Johns Hopkins School of Medicine, and the National Cancer Institute.

With this acquisition, Kiromic will bring in-house a team of experts in bioinformatics and AI in order to lengthen its lead in the race for an AI technology with the capability to select the optimal bio-markers needed for cutting edge immunotherapeutics such as CAR-T cell therapy.

Many CAR-T developers are still developing their CAR-T with biomarkers from decade old target libraries with known poor clinical outcomes.

Chief Executive Officer of Kiromic, Maurizio Chiriva-Internati, DBSc, PhDs, commented

We are pleased to have officially closed this long awaited acquisition of InSilico Solutions.

The InSilico Solutions is another testament to our commitment to developing the very best possible CAR-T. And the very best CAR-T will start with having the best possible bio-markers by employing cutting edge bio-informatics and AI technologies.

Our CAR-T will be outpatient, off-the-shelf allogeneic.

The amount of information that oncologists and scientists gather from cancer patients continues to grow exponentially.

The number of scientists and the time those scientists have to analyze those billions of data point have not grown exponentially.

It makes sense that bioinformatics and artificial intelligence are brought to bear on the tasks of going through the mountains of data to select biomarkers in a few hours which would have required decades of human labor to do.

Best bio-informatics and AI.

Better biomarkers.

Better Manufacturing.

Better CAR-Ts.

Better Clinical Outcomes.

Chief of BioInformatics and Research Computing Officer, Michael Ryan, PhD commented :

Over the past 3 years we have had an amazingly productive collaboration with Kiromic.

Together we produced a highly effective system that allows Kiromic to identify the needles in the haystack of genomic data – small sections of protein that are specific to the surface of cancer cells and that can be targeted by immunotherapy.

The entire InSilico staff is extremely energized by the acquisition by Kiromic.

We believe we can have an immediate, significant impact on accelerating delivery of effective treatment to patients.

Our next focus will be on utilizing AI methods to optimize response to allogeneic T cell therapy.

In particular, we are developing models using WGS, RNASeq, scRNASeq, cytrometry, and cytokine panels to assist in selecting donor T cells with the strongest therapeutic potential.

Similar data from clinical trials will be used refine our understanding of efficacy and toxicity to improve treatment protocol and patient selection.

We will continually evaluate, implement, and improve our industry leading systems that will accelerate therapeutic development, manufacturing, and clinical testing of Kiromic’s off-the-shelf allogeneic CAR-T for solid tumors.

Chief Medical Officer of Kiromic, Scott Dahlbeck, MD commented:

World-wide, patients with advanced cancer conditions are in great need of effective treatment solutions that can be added to the clinical armamentarium of medical providers.

However, in order to achieve significant gains in patient survival, innovative discoveries in biomarker discovery, selection, and validation are critical to facilitate the development of the next generation of immunotherapeutics that can truly make a difference.

The acquisition of InSilico Solutions is a major step forward in this process, and we are looking forward to the breakthroughs that will result from this expansion of Kiromic’s AI capabilities and subsequently its CAR-T.

Chief of Strategy and Innovation Officer, Mr. Gianluca Rotino commented:

The acquisition of InSilico will allow significant advancement in the use of computational technologies throughout the development process, from discovery to manufacturing and in clinical trials.

This places Kiromic among the pioneers in innovative cell therapy and makes the upcoming clinical trial a critical milestone not only for the company, but for all the Cell Therapy Space.

Under the agreement terms, Kiromic acquires InSIlico through a stock-swap operation, hiring the entire staff of InSIlico and their material and immaterial assets.

The deal was followed up by the Strategy and Corporate Development department of Kiromic Biopharma

BEVILACQUA LLP served as Legal Counsel.

ThinkEquity served as financial advisors. ThinkEquity, a division of Fordham Financial Management, Inc.

Chief Financial Officer, Mr. Tony Tontat commented:

InSilico Solutions was a great find for the company 3 years ago when the collaboration started.

It’s an even better find today with the closing of this acquisition.

InSilico in-house will mean that our bio-informatics department will have the continuous attention of developers as new developments evolve.

The InSilico acquisition will not impact the company’s cash runway post the recent follow-on financing which closed on July 2021.

On July 26, 2021 ImmunoMet Therapeutics, Inc., a clinical stage biotechnology company targeting metabolism to develop novel anti-fibrotic and anti-cancer therapies, reported that Dr. Revati Shreeniwas has joined the company as Chief Medical Officer (Press release, ImmunoMet Therapeutics, JUL 26, 2021, View Source [SID1234585201]). In this role, Dr. Shreeniwas will manage the clinical development program for ImmunoMet’s lead product candidate, IM156, an investigational Protein Complex 1 (PC1) inhibitor, being evaluated for idiopathic pulmonary fibrosis (IPF) and oncology indications.

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"Earlier this month we finished dosing our US Phase 1 study of IM156 in healthy volunteers. ImmunoMet is now positioned to advance the clinical development of IM156 in IPF patients. Dr. Shreeniwas brings a wealth of clinical experience to ImmunoMet including extensive IPF clinical experience," said Dr. Benjamin Cowen, President and CEO of ImmunoMet Therapeutics.

Dr. Shreeniwas is a physician certified in internal medicine and pulmonary disease with 17 years of experience in pharmaceutical development. She has designed and implemented more than 50 US and international (Phase 1-4) clinical trials, and been the clinical lead for regulatory interactions with the FDA and EMA. Dr. Shreeniwas has worked on several commercially successful drugs. She has served on the faculty of Stanford University and Columbia Presbyterian Medical Center. Prior to entering pharmaceutical industry Dr. Shreeniwas practiced clinical medicine for 15 years. She is licensed to practice medicine in California. Dr. Shreeniwas graduated from Armed Forces Medical College, India.

"ImmunoMet is positioned to make significant progress in clinical development in IPF and oncology indications. I am especially pleased to be joining the leadership team at this pivotal moment in the company’s history," said Dr. Shreeniwas. "The company’s research to date indicates that IM156 has a unique profile and the potential to offer significant benefit to patients."

About IM156

IM156 is a Protein Complex 1 (PC1) inhibitor that targets the oxidative phosphorylation (OXPHOS) pathway, decreasing the supply of energy and anabolic precursors that are required to drive fibrotic disease and tumor growth. IM156, ImmunoMet’s lead drug candidate, is solely owned by ImmunoMet and is currently in development for the treatment of IPF and selected cancers.

On July 26, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that it has entered into a note purchase agreement with a fund of Athyrium Capital Management, LP, a specialized asset management company focused on opportunities in the global healthcare sector, for the issuance of up to $125 million of notes thereunder, subject to funding in two tranches (Press release, Puma Biotechnology, JUL 26, 2021, View Source [SID1234585200]).

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Puma received gross proceeds of $100 million from the first tranche of notes issued by Puma under the note purchase agreement upon closing on July 23rd and intends to use the funds, together with cash on hand, to retire its existing loan with Oxford Finance LLC. The second tranche of $25 million may be drawn at a later date; if drawn down these proceeds would be used for general corporate purposes and to further support NERLYNX commercial initiatives. Armentum Partners served as the Company’s financial advisor in connection with the note purchase agreement. The notes will become due in July 2026. Additional information on the note purchase agreement will be filed with the Securities and Exchange Commission as a Current Report on Form 8-K.

Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to enter into this note purchase transaction with Athyrium Capital and to have their support with the continued commercialization of NERLYNX. This financing will be used to continue to support NERLYNX commercial activities as well as ongoing research with neratinib."

"We are excited to partner with Puma Biotechnology in supporting NERLYNX in its current indications, as well as its clinical development programs for additional indications," said Laurent D. Hermouet, Partner at Athyrium. "With the Company’s track record of in-licensing successes, we are also thrilled at the potential to help finance inorganic growth activities as they may present themselves to the Company."