On March 31, 2022 Hummingbird Diagnostics GmbH, a leader in reading blood-based microRNAs for early disease detection and characterization, reported the publication of a study in the journal npj Precision Oncology that describes the discovery and validation of miRisk, a first-of-its-kind microRNA (miRNA) biomarker signature that offers the prospect of a blood-based companion diagnostic for immunotherapy in advanced non-small cell lung cancer (NSCLC) (Press release, Hummingbird Bioscience, MAR 31, 2022, View Source [SID1234611312]). The results of the study illustrate the development of miRisk and its prognostic value for overall survival following immunotherapy. The blood-based test holds the potential for broad applicability for the management of patients with cancer.

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Biomarkers have been shown to help identify patients who are most likely to benefit from treatment with immunotherapies, such as PD-1/PD-L1-targeted therapies. Still, the gold standard of tumor tissue PD-L1 staining, as well as other biomarkers, such as tumor mutational burden, do not always accurately predict the efficacy of these therapies in patients. Immune cell-derived miRNAs reflect physiological and pathophysiological processes and can be sampled from peripheral blood. miRNAs are short non-coding RNAs that act as molecular rheostats that exercise control over the expression of most human genes. miRNAs are relatively accessible yet reflect complex underlying biology, offering the prospect of a blood-based companion diagnostic to determine the best candidates for immunotherapy.

"Immunotherapy has revolutionized the treatment of non-oncogene-driven advanced cancers, yet only approximately 30 percent of patients respond favorably to these treatments. Determining which patients will respond to these powerful therapies represents one of the greatest needs in oncology," said Bruno Steinkraus, PhD, Chief Scientific Officer of Hummingbird Diagnostics and leader of the published research. "This study illustrates the potential of how miRNAs taken from peripheral whole blood can be analyzed to predict the efficacy of PD-(L)1-targeted therapies in patients with NSCLC and improve patient outcomes. We thank all of our collaborators and patients for their vital contributions to this research."

The work, led by Hummingbird, was part of a collaboration with Priv.-Doz. Petros Christopoulos, MD, and Prof. Michael Thomas, MD, of the Thoraxklinik at Heidelberg University Hospital, as well as Prof. Martin Reck, MD, of the LungenClinic Grosshansdorf.

"Patient stratification — identifying who will benefit from treatment and who will likely fail to respond or even come to harm due to adverse events — remains challenging, and there is pressing need for more accurate biomarkers for immunotherapy response prediction," said Jochen Kohlhaas, Founder and Chief Executive Officer of Hummingbird Diagnostics. "This work could broaden our general understanding of tumor immunobiology and, if validated, offers several important opportunities to improve management and outcomes of patients with advanced NSCLC and possibly other cancers."

Based on an analysis of whole blood miRNA profiling of 3 well-characterized cohorts consisting of a total of 334 stage IV NSCLC patients, the team discovered and validated a 5-microRNA risk score (miRisk) that is prognostic of overall survival following immunotherapy of either pembrolizumab or nivolumab. In a head-to-head comparison of miRisk and the gold standard PD-L1 tumor proportion score (TPS), the authors report superior diagnostic performance of miRisk compared to PD-L1 status. Of note, the miRNA signature does not require tumor tissue and could thus be employed in an off-the-shelf manner. The identified biomarker signature was traced back to a myeloid origin, especially neutrophils and macrophages, and miRNA target prediction was performed to identify a potential direct mechanistic link to the PD-L1 signaling pathway and PD-L1 itself. One example of a potential first clinical application is the selection of PD-L1-high patients for either single agent immunotherapy or chemo-immuno combination therapy where presently both options are licensed. In addition, miRisk measurements might provide a tissue-independent way of identifying by current standards ineligible patients who may benefit from immuno-monotherapy.

The open-access article can be found online on the journal’s website: View Source

On March 31, 2022 Numab Therapeutics AG ("Numab") and Ono Pharmaceutical Co., Ltd. ("Ono") reported that Ono has exercised its option to enter into a development and license agreement for a multispecific antibody candidate that was generated through a research collaboration between the two companies initiated in 2017 (Press release, Numab, MAR 31, 2022, View Source [SID1234611311]). Under the terms of the license agreement, Ono acquires intellectual property rights and exclusive global development and commercialization rights for a multispecific antibody targeting a novel immuno-oncology target. In consideration for the discovery work and the license, Numab will receive up to CHF 258 million in research funding, upfront and milestone payments plus tiered single to double digit royalties on future sales.

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"We are proud to have advanced this novel multispecific antibody candidate against a new and very challenging immuno-oncology target to this milestone," said David Urech, Ph.D., Founder and Chief Executive Officer of Numab. "The licensing of the asset is an affirmation of our platform’s ability to create novel and unique pharmacology. We look forward to our continued partnership with Ono as we have been further collaborating on our shared mission of developing next generation immuno-oncology therapeutics for patients with cancer."

"We hope that the program candidate generated through our work with Numab will become a therapeutic option for patients with cancer who may benefit from this new treatment modality," said Toichi Takino, Senior Executive Officer / Executive Director, Discovery & Research of Ono Pharmaceutical. "Through the synergy between Numab’s multispecific antibody platform and Ono’s deep immuno-oncology expertise, we are continuously committed to fueling our diverse drug discovery efforts to advance our immuno-oncology pipeline."

In March 2020, Numab and Ono expanded their alliance by executing a second research and option agreement to discover and develop a multispecific antibody drug candidate for the treatment of various cancers.

On March 31, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that the European Medicines Agency (EMA) has granted obe-cel, Autolus’ leading CAR T clinical candidate, Orphan Medical Product Designation for treatment of acute lymphoblastic leukemia (ALL) patients (Press release, Autolus, MAR 31, 2022, View Source [SID1234611309]).

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"This regulatory designation is an important milestone toward addressing the urgent, unmet need in ALL patients, and follows the Orphan Drug Designation previously granted in 2019 by the U.S. Food and Drug Administration (FDA) for obe-cel," said Dr. Christian Itin, Chief Executive Officer of Autolus. "Recruitment is ongoing in the Phase 2 portion of the pivotal study of obe-cel and we look forward to announcing first Phase 2 data this year."

Orphan Medical Product Designation is granted by the EMA Committee for Orphan Medicinal Products to medicines intended for the treatment, diagnosis or prevention of a disease that is life-threatening or chronically debilitating that affects fewer than 5 in 10,000 people in the EU under the Orphan Regulation (Regulation (EC) No 141/2000). To attain Orphan Designation, it must be justified that a medicinal product could potentially be of significant benefit compared to the existing authorized medicinal products for those affected by the condition. Benefits of the designation include fee reductions for centralized activities including; applications for marketing authorization, inspections and scientific advice. A key benefit is ten years of market exclusivity in the EU following marketing approval by the EMA.

On March 31, 2022 Savara Inc. (Nasdaq: SVRA), an orphan lung disease company, reported financial results for the fourth quarter and full year ending December 31, 2021 and provided a business update (Press release, Savara, MAR 31, 2022, View Source [SID1234611306]).

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"The company underwent a significant amount of positive change in 2021. We streamlined the pipeline to focus solely on the molgramostim development program, strengthened our management team with key hires in clinical, regulatory, and CMC and improved our financial position with a $130M equity raise," said Matt Pauls, Chair and CEO, Savara. "With a cash position of ~$161M at the end of 2021, and a track record of fiscal discipline, we believe we are funded through 2025 – which is well beyond the anticipated top line read-out of IMPALA-2, our pivotal Phase 3 clinical trial in aPAP. We continue to advance the IMPALA-2 trial with most of the approximately 50 clinical trial sites now activated, and despite the ongoing COVID-19 pandemic and current geopolitical issues impacting parts of Europe, we reaffirm our guidance of top line data by the end of 2Q 2024."

Fourth Quarter Financial Results (Unaudited)

Savara’s net loss for the fourth quarter of 2021 was $11.3 million, or $(0.07) per share, compared with a net loss of $13.7 million, or $(0.23) per share, for the fourth quarter of 2020.

Research and development expenses were $7.6 million for the fourth quarter of 2021, compared with $10.2 million for the fourth quarter of 2020.

General and administrative expenses for the fourth quarter of 2021 and 2020 were $3.0 million and $2.8 million, respectively.

As of December 31, 2021, the Company had cash, cash equivalents and short-term investments of $161.2 million.

Fiscal Year 2021 Financial Results

The Company’s net loss for the year ended December 31, 2021 was $43.0 million, or $(0.32) per share, compared with a net loss of $49.6 million, or $(0.84) per share for the year ended December 31, 2020.

Research and development expenses decreased $6.0 million, or 17.3%, to $29.0 million for the year ended December 31, 2021 from $35.0 million for the year ended December 31, 2020. The decrease was largely attributable to $5.4 million of acquisition costs for the inhaled ciprofloxacin product candidate (in 2020) and a $6.9 million decrease in Chemistry, Manufacturing, and Controls (CMC) and clinical operations activities associated with the wind down of the inhaled vancomycin study. This was partially offset by a $6.4 million increase in costs associated with the startup and progression of the IMPALA-2 trial.

General and administrative expenses decreased $1.9 million, or 13.4%, to $12.4 million for the year ended December 31, 2021 from $14.3 million for the year ended December 31, 2020. The decrease was primarily due to the recognition of a one-time non-recurring charge of $0.8 million for non-cash stock-based compensation and approximately $1.5 million of paid and accrued severance payments to former members of the Company’s executive management during the year ended December 31, 2020.

On March 31, 2022 Portage Biotech Inc. (NASDAQ: PRTG) ("Portage" or the "Company"), a clinical-stage immuno-oncology company developing therapies to improve patient lives and increase survival by avoiding and overcoming cancer treatment resistance, reported its development goals for the remainder of 2022 (Press release, Portage Biotech, MAR 31, 2022, View Source [SID1234611304]).

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"We are pleased to report that as expected, Portage’s invariant natural killer T cell (iNKT) agonists, PORT-2 and PORT-3, were well tolerated in initial clinical studies," said Dr. Ian Walters, chief executive officer of Portage. "We believe that robust randomized trial design approaches for both PORT-2 and PORT-3 will allow us to rapidly evaluate efficacy signals in Phase 2. With our unique drug development strategy, experienced management team, burgeoning collaborations with academic and pharma partners and financial resources secured in 2021, Portage is well prepared and funded to leverage our product engine to deliver on important clinical milestones through the end of 2023."

Q2-Q4 2022 Development Focus

The Company remains focused on advancing its pipeline of novel immuno-oncology therapeutics designed to prevent and overcome cancer treatment resistance. Clinical trials were initiated in 2021 for both of Portage’s lead invariant natural killer T cell (iNKT) agonist programs, PORT-2 (a liposomal formulation iNKT agonist) and PORT-3 (a nanoparticle coformulation of Portage’s iNKT agonist packaged with an antigen to establish immune priming and boosting).

Preliminary Phase 1 data received to date suggests PORT-2 was well tolerated when administered as a monotherapy, with no related adverse events. This has enabled a plan to accelerate opening of the combination safety cohort with Keytruda, in parallel with the ongoing high dose monotherapy cohort. Detailed data will be submitted to congresses later this year.

With the enhanced management team, efficient organization, and financial resources obtained in 2021, Portage has decided to expand the PORT-2 study beyond the UK to accelerate clinical studies while addressing COVID-19 headwinds. The Company has hired a global clinical research organization (CRO-Parexel) and is preparing for regulatory submissions in other countries. By expanding the regions and sites contributing to the study, Portage will be enabled to accelerate enrollment in the planned Phase 2 portion of this trial.

Preliminary safety data for repeat dosing of PORT-3, a nanoparticle co-formulation of PORT-2 and NY-ESO-1 immunogenic peptides developed for the treatment of NY-ESO-1 positive solid tumors, is also favorable. The Company expects to submit data to a scientific congress for PORT-3 later this year.

New Collaborations with Academic Partners to Enhance Strategic Goals

As part of its broader research and development strategy, Portage is partnering with experts and companies that could bring additional expertise and insights to help advance the science and open new avenues for development. New collaborations include a partnership with Dr. Francis Mussai and Dr. Carmela De Santo at University of Birmingham on iNKTs. Dr. Mussai and colleagues will be analyzing samples for immune markers and helping Portage to understand both the pro-inflammatory markers induced by iNKT agonists as well as the impact on suppressive cells that can impair immune based attacks.

Portage is also initiating a second collaboration with Dr. Robert Negrin and his team at Stanford University to evaluate the use of PORT-2 with iNKT cell therapies in animals. This work will evaluate if an agonist co-administered with expanded or transformed iNKT cells can further activate the transplanted and endogenous cells inside the patient. The Stanford collaboration will also study the impact iNKT agonists have on driving an adaptive immune response and correcting the suppressive tumor microenvironment.

Clinical Development Goals for the Remainder of 2022

Generate safety and efficacy data on all products currently in clinical trials
PORT-2: iNKT agonist to treat melanoma and non-small cell lung cancer (NSCLC) (Phase 1/2); initial efficacy data anticipated by the end of 2022
PORT-3: iNKT agonist co formulated in a nanoparticle with NY-ESO-1 peptide vaccine in tumors that express NY-ESO-1 (Phase 1/2); preliminary efficacy data in patients expected year end, going into 2023
PORT-1: intratumoral amphiphilic formulation, developed in collaboration with our affiliate Intensity, being evaluated as a monotherapy and in combination with Keytruda and Yervoy to treat multiple solid tumors (Phase 2); multiple readouts expected in 2H 2022
Prepare additional compounds to enter clinical studies
PORT-5: Systemically delivered STING agent developed in collaboration with our affiliate Stimunity, is progressing towards the clinic. Preclinical data has been recently published and was selected for a late breaker presentation at the 2022 American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. This compound is a next generation, systemically delivered, targeted STING approach differentiated from others in this area.
Continue to explore collaboration opportunities for all of our assets and evaluate new opportunities to expand immuno-oncology product portfolio
"We are grateful to the patients and families who have enrolled in our studies and are helping us to better understand cancer and ways to improve care. While the COVID pandemic has certainly created challenges for everyone, Portage is optimistic moving in to 2022 that we can resume more normal activities in our day-to-day business. The Company’s focus for this year is on data generation and ways to accelerate the studies that were initially managed by third parties. With this lean structure, our current financial runway is sufficient to support progress through the end of 2023 including the release of many key data points from our ongoing trials," concluded Dr. Walters.