On February 15, 2022 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells directly within the patient’s body, reported that the company’s therapeutic Immuno-STAT (Selective Targeting and Alteration of T cells) biologics are scheduled to be featured in an Oxford University poster presentation at the Biophysical Society Annual Meeting taking place on February 19-23, 2022 at the Moscone Center in San Francisco, California (Press release, Cue Biopharma, FEB 15, 2022, View Source [SID1234608264]). Cue Biopharma entered into a strategic research collaboration with Dr. Michael Dustin and the University of Oxford in May 2020 to determine the molecular mechanisms underlying the activity of its IL-2 based CUE-100 series biologics.

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Presentation Details
Title: Integration of IL-2 Signaling at the Immunological Synapse
Presenter: Dr. Jesusa Capera Aragones of the Kennedy Institute at the University of Oxford
Poster Session: Membrane Receptors and Signal Transduction
Poster #: 414/B238
Poster Location: Exhibit Hall ABC
Date & Time: February 20, 2022 at 1:45 p.m. PST or 4:45 p.m. EST

"It has traditionally been the view that cytokine signaling follows T cell receptor signaling, however this study demonstrates that antigen-T cell receptor signaling and cytokine signaling can work side-by-side to impact T cell responses through the immunological synapse," said Dr. Dustin, professor of immunology and Wellcome Trust Principal Research Fellow, director of research of the Kennedy Institute at the University of Oxford.

Dr. Anish Suri, president and chief scientific officer of Cue Biopharma commented, "The mechanistic insights provided by the elegant work conducted by Dr. Aragones and Dr. Dustin supports the central hypothesis of Immuno-STATs specifically – that concurrent delivery of antigen and interleukin 2 (IL-2) signals results in robust synapse formation, providing for selective T cell activation, a supposition now being clinically validated through the development of CUE-101, our lead and representative IL-2 based drug product candidate from the CUE-100 series."

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

About Immuno-STAT
The company’s Immuno-STAT (Selective Targeting and Alteration of T cells) biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a pMHC to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-stimulatory signaling molecule to modulate the activity of the target T cells.

The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in selective T cell modulation. Because our drug candidates are delivered directly in the patient’s body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients’ T cells to be extracted, modified outside the body (ex vivo), and reinfused.

On February 15, 2022 Champions Oncology, Inc. (NASDAQ:CSBR), a leading global technology-enabled biotech that is transforming drug discovery through innovative AI-driven pharmaco-pheno-multiomic integration, reported a co-development partnership with GigaMune (Press release, Champions Oncology, FEB 15, 2022, View Source [SID1234608121]). The partnership will combine Champions’ novel Autologous Tumor Infiltrating Lymphocyte (TIL) platform with GigaMune’s T Cell Receptor (TCR) Discovery platform to accelerate the development of next generation T cell therapies and cancer diagnostics, through the identification of novel TCR sequences.

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The planned partnership will leverage GigaMune’s proprietary TCR discovery and validation workflow to create a library of natively paired TCR sequences derived from Champions’ Autologous TIL platform. The combination of Champions’ unique autologous systems with GigaMune’s proprietary discovery workflow will scale-up the ability to screen for novel TCR sequences, otherwise limited by the availability of TILs, while enabling the identification of rare-antigen reactive TCRs. The outcome of this effort will be unique functionally characterized libraries of TCRs. This TCR library will then be used to further the development of next generation T cell therapies and non-invasive early detection diagnostics, with a focus on solid tumor indications. Under the terms of the agreement, Champions will have the right to select a specified number of TCRs from the library for further, wholly owned, development. The remaining libraries will be jointly owned by Champions and GigaMune for commercialization, with commercial efforts led by Champions.

Ronnie Morris, MD, President and CEO of Champions Oncology, said "Our immune system is capable of recognizing and eliminating cells that have become infected or damaged as well as those that have become cancerous. Cellular or cancer immunotherapy therapy, is a form of treatment that uses the cells of our immune system to eliminate cancer and has brought significant improvements for cancer patients in terms of survival and quality of life and is considered a novel pillar of cancer care. Our unique Autologous TIL platform has expanded our knowledge of the complex interplay between the immune system and tumor cells. We’ve used the platform to better understand TIL biology, mechanisms of immune killing, and the confirmation novel intrinsic mechanisms of immune evasion. We’ve always envisioned that this platform could one day be used for discovery efforts, and this partnership with GigaMune will help to make that a reality. With these TCR libraries co-developed with GigaMune, we plan to explore the possible development of novel cell therapies, expand upon our early detection efforts, and commercialize the bulk of the TCR libraries through partnerships and our Lumin platform. We’re excited to see how this partnership might contribute to the progress of these efforts."

"We’re excited to partner with Champions to use world-leading GigaMune TCR discovery technologies to hunt for tumor-reactive TCRs in more TIL samples," said David Johnson, CEO of GigaMune. "Over the years we’ve found that getting the right samples is as important as having the right screening technology, so this project is a perfect partnership for success."

On February 15, 2022 Ipsen (Euronext: IPN; ADR: IPSEY) reported that two-year (25.4 months minimum; 32.9 months median) follow-up results from analyses of the Phase III CheckMate -9ER trial, which demonstrated sustained survival and response rate benefits (abstract #350)1, as well as health-related quality of life (HRQoL) improvements (abstract 323)2, with the combination of Cabometyx (cabozantinib) and Opdivo (nivolumab) versus sunitinib in the first-line treatment of advanced renal cell carcinoma (aRCC) (Press release, Ipsen, FEB 15, 2022, View Source;9ER-Trial [SID1234608138]). These updated results will be featured in two poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) from February 17 to 19, 2022.

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Dr. Cristina Suárez, M.D. PhD, Medical Oncologist at the Vall d´Hebron University Hospital, Barcelona, Spain and a lead investigator on the Phase III CheckMate -9ER trial said, "I am delighted to see the extent of the efficacy benefits demonstrated with the combination of Cabometyx and Opdivo in the CheckMate -9ER trial. These new data showcase the possibilities we can offer patients for their advanced disease, presenting the opportunity to significantly reduce their risk of death, and for some patients, achieve a complete response, whilst maintaining quality of life. There has been a dramatic evolution in the treatment landscape across lines of therapy for people living with renal cell carcinoma over recent years; this is an exciting time to be a treating physician in this area."

With a median follow-up of 32.9 months (25.4 months minimum), Cabometyx in combination with Opdivo continued to show superiority across efficacy endpoints of overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), including increased complete response (CR) rates compared to sunitinib.1 For the secondary endpoint of median OS, the combination demonstrated a maintained clinically meaningful improvement (37.7 months vs. 34.3 months), with a 30% reduction in the risk of death (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.55 to 0.90) compared to sunitinib.1 PFS benefits, the primary endpoint of the study, were also maintained, with the combination continuing to double median PFS vs. sunitinib (16.6 months vs. 8.3 months, respectively; HR: 0.56; 95% CI: 0.46 to 0.68).1 Additionally, both superior ORR and DCR benefits were shown to be sustained with increased follow-up for the combination versus sunitinib; ORR 55.7% vs 28.4% and DCR 88.2% vs 69.3%. Moreover, among patients treated with the combination, 12.4% had a complete response vs 5.2% for sunitinib.1 In a further exploratory analysis of depth of response in target lesions by organ site, a higher percentage of patients experienced tumor shrinkage benefits with Cabometyx in combination with Opdivo vs. sunitinib across all organ sites assessed (kidney, liver, lung, lymph node and bone).1

The safety profile identified in the CheckMate -9ER trial was consistent with that previously observed for Cabometyx and Opdivo. 97.2% of patients treated with the combination experienced a treatment-related adverse event (TRAE) of any grade, compared to 93.1% of patients treated with sunitinib.1 Overall, 10.6% discontinued Opdivo only, 9.1% discontinued Cabometyx only, and 7.5% discontinued both Cabometyx and Opdivo (simultaneously or sequentially).1

In a separate analysis, with 32.9 months median follow-up, patients continued to report clinically meaningful HRQoL benefits with Cabometyx in combination with Opdivo compared to sunitinib.2 These exploratory outcomes were measured using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) which assessed quality of life (QoL) associated specifically to kidney cancer as well as EQ-5D-3L instruments which assessed QoL more generally. HRQoL scores from these instruments were found to be improved or maintained over time amongst patients treated with the combination, while reductions in scores were observed with sunitinib. Additionally, those who received the combination were 48% less likely to be notably bothered by treatment side effects than patients in the sunitinib arm.2 These updated data follow the publication of 23.5 month median follow-up HRQoL data in The Lancet Oncology, published on 12 January 2022.3

Steven Hildemann, M.D. PhD, Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Global Patient Safety, Ipsen said, "These new data from the CheckMate -9ER trial build on the previously demonstrated sustained efficacy benefits of the combination of Cabometyx and Opdivo, across patient risk groups. We are delighted to see that these extended survival benefits are further supported by a continued maintenance of health-related quality of life. Evaluating the patient perspective has been an integral element of the CheckMate -9ER trial analyses, ensuring that data are representative of the patient population and their priorities. With this growing body of evidence for the combination of Cabometyx and Opdivo, we are confident of the potential for these data to be realized in real world settings worldwide."

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

ENDS

About renal cell carcinoma (RCC)
There were over 400,000 new cases of kidney cancer diagnosed worldwide in 2020.4 Of these, RCC is the most common type of kidney cancer, accounting for approximately 90% of cases.5,6 It is almost twice as common in men, and male patients account for over two thirds of deaths.4 If detected in the early stages, the five-year survival rate is high, but for people living with advanced or late-stage metastatic RCC, the survival rate is much lower, around 12%, with no identified cure for this disease.7,8

About the CheckMate -9ER trial
CheckMate -9ER was an open-label, randomized, multi-national Phase III trial evaluating people living with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). The secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis compared the doublet combination versus sunitinib in all randomized patients. The trial was sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)
In the U.S., Cabometyx tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. Outside the U.S., Cabometyx is currently approved in 60 countries, including in the European Union, Great Britain, Norway, Iceland, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong Kong, Singapore, Macau, Jordan, Lebanon, the Russian Federation, Ukraine, Turkey, the United Arabic Emirates (U.A.E.), Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Malaysia, Colombia and Egypt for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, Great Britain, Norway, Iceland, Canada, Australia, New Zealand, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, the Russian Federation, Ukraine, Turkey, the U.A.E., Saudi Arabia, Israel, Serbia, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Egypt and Malaysia for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, Great Britain, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, the Russian Federation, Ukraine, Turkey, Lebanon, the U.A.E., Peru, Panama, Guatemala, Chile, the Dominican Republic, Ecuador, Thailand, Brazil, New Zealand, Egypt and Malaysia for HCC in adults who have previously been treated with sorafenib. Cabometyx is also approved in combination with nivolumab as first-line treatment for people living with advanced RCC, in the European Union, Great Britain, Norway, Iceland, Switzerland, Taiwan, Singapore, the U.A.E., Australia, Chile, Israel and the Russian Federation.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC) and in the U.S. Prescribing Information (USPI).

Ipsen has exclusive rights for the commercialization of Cabometyx outside the U.S. and Japan. Cabometyx is marketed by Exelixis, Inc. in the U.S. and by Takeda Pharmaceutical Company Limited in Japan. Cabometyx is a registered trademark of Exelixis, Inc.

On February 15, 2022 Medivir reported that Year-End Report, January – December 2021 (Press release, Medivir, FEB 15, 2022, View Source;year-end-report-january–december-2021-301482292.html [SID1234608155])

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October – December

Financial summary for the quarter

Net turnover amounted to SEK 13.9 (1.5) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -23.5 (-10.6) million. Basic and diluted earnings per share amounted to SEK -0.44 (-0.46) and SEK -0.44 (-0.46) respectively.
Cash flow from operating activities amounted to SEK -5.4 (-1.0) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 221.2 (70.0) million.
Significant events during the quarter

In October, the Board of Directors appointed Jens Lindberg as new CEO of Medivir. Jens Lindberg has extensive experience from the pharmaceutical industry and the field of Oncology. He joins from Sedana Medical where he has been VP Commercial Operations and acting CEO.
IGM Biosciences, Inc. initiated its clinical study in solid cancers with birinapant (IGM-9427) in combination with IGM’s DR5 agonist antibody IGM-8444. The purpose of this first clinical trial with the combination is to evaluate safety and tolerability.
In November, results from an investigator-initiated phase II clinical trial of remetinostat in patients with squamous cell carcinoma were published.
In December, it was announced that the first patient with hepatocellular carcinoma had started treatment with fostroxacitabine bralpamide (MIV-818) in the phase 1b / 2a combination study.
January – December

Financial summary for the period

Net turnover amounted to SEK 25.5 (13.9) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -59.5 (-38.5) million. Basic and diluted earnings per share amounted to SEK -1.20 (-1.75) and SEK -1.20 (-1.75) respectively.
Cash flow from operating activities amounted to SEK -48.7 (-58.1) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 221.2 (70.0) million.
Significant events after the end of the period

In January, it was announced that the WHO had selected fostroxacitabine bralpamide as the official generic name for the patented candidate drug MIV-818, which is in clinical development in primary liver cancer.
Jens Lindberg assumed his position as CEO of Medivir on January 24, 2022.
Conference call for investors, analysts and the media

The Year-End Report January – December 2021 will be presented by Medivir’s CEO, Jens Lindberg.

The conference call will also be streamed via a link on the website: www.medivir.com

The presentation will be available on Medivir’s website after completion of the conference.

CEO’s message

On January 24, 2022, I took over as CEO of Medivir and after my first time on the job, it is clear to me why the company managed to deliver so well on business goals in 2021. We have an extremely competent and experienced team that works dedicatedly with both our cutting-edge project fostroxacitabine bralpamide (MIV-818) and with the business development for our other assets. I hope to be able to contribute to the further strengthening of our delivery capacity in the future. Under the leadership of the company’s former CEO Yilmaz Mahshid, today a board member of Medivir, and our CFO Magnus Christensen, who has been the company’s interim CEO since May, Medivir has made significant progress in 2021.

Medivir’s drug development focuses on a very promising and proprietary clinical project, fostroxacitabine bralpamide (formerly MIV-818), with a clear therapeutic target, where the unmet medical needs remain extremely large, despite recent clinical advances. Fostroxacitabine bralpamide has the potential to become the first liver-targeted and orally administered drug that can help patients with various cancers of the liver. Its unique mechanism of action means that it does not directly compete with other treatment options but instead enables combination treatments with other drug alternatives in hepatocellular carcinoma (HCC). Liver cancer is the third leading cause of cancer-related deaths worldwide and HCC is the most common form of cancer that arises in the liver. The effect of today’s medications is often limited and mortality remains at a high level.

After the end of the year, MIV-818 received the official generic name fostroxacitabine bralpamide from the World Health Organization WHO, something we see as an important step towards a product for the treatment of HCC.

The clinical development program for fostroxacitabine bralpamide has passed a number of milestones during the year. In April, it was announced that the top-line results from the monotherapy part of the phase Ib study were positive with a good safety and tolerability profile. They were later presented in more detail at the ESMO (Free ESMO Whitepaper) Congress in September and aroused great interest. In May, the design for the next step, the phase 1b/2a combination study with fostroxacitabine bralpamide for liver cancer, was presented. The regulatory approval from the British Medicines & Healthcare products Regulatory Agency (MHRA) for the study was obtained at the end of August, and from the South Korea Ministry of Food and Drug Safety (MFDS) in November.

In December, the first patient with HCC was dosed in the phase 1b/2a combination study with fostroxacitabine bralpamide, which is given in combination with two other medicines, either with Lenvima, a tyrosine kinase inhibitor, or with Keytruda, an anti-PD-1 checkpoint inhibitor. Lenvima and Keytruda (approved in the USA) are currently approved as mono therapy treatments of HCC.

The licensing agreement with IGM Biosciences, Inc., which gives IGM the global and exclusive rights to develop birinapant, could potentially provide milestone payments up to a total of approximately USD 350 million as well as tiered royalties up to "mid-teens". At the time of signing in January 2021, Medivir received USD 1 million, and when IGM in early November initiated a phase I clinical trial in solid cancers with birinapant in combination with its own DR5 agonist antibody IGM-8444, it was followed by an additional USD 1.5 million. Of course, we look forward to IGM’s continued clinical development of birinapant.

Also for remetinostat, a number of steps forward made during the year should be noted. Positive results from the investigator-initiated phase II clinical trial of remetinostat in patients with squamous cell carcinoma were published in November in the scientific journal JAMA Dermatology. Promising results from the investigator-initiated phase II study with remetinostat for basal cell carcinoma were published in August in the scientific journal Clinical Cancer Research. Through a renegotiated multi-party agreement, Medivir was able to further strengthen the business development potential for remetinostat in August.

Business development and collaborations are central to Medivir’s success. Birinapant is a good example of this and we see opportunities for remetinostat and MIV-711, but also in other smaller projects. In early 2021, a licensing agreement was entered into with Ubiquigent for the preclinical research program USP7.

Thanks to the financing that was successfully carried out at the beginning of the year and provided the company with approximately SEK 223 million before transaction costs, we are entering 2022 with resources and business development opportunities that provide good conditions for continuing the clinical development program for our cutting-edge project fostroxacitabine bralpamide. Our goal is to make it an effective drug for liver cancer that makes a real difference for patients and for healthcare, and thus also for our shareholders. I look forward to keeping you informed about Medivir’s continued development.

On February 15, 2022 (the "Effective Date"), Cue Biopharma, Inc. (the "Company") reported that entered into a loan and security agreement (the "SVB Loan Agreement") with Silicon Valley Bank, as lender ("SVB"), pursuant to which SVB has agreed to provide term loans to the Company in an aggregate principal amount of up to $20.0 million (the "SVB Term Loans"), consisting of (i) a tranche A term loan in the aggregate principal amount of $10.0 million, available to the Company on or around the Effective Date, and (ii) two contingent tranche B term loans in amounts of at least $5.0 million each and in an aggregate principal amount not to exceed $10.0 million, available to the Company at any time on or prior to December 31, 2022, following the Company having received both (x) positive data for the CUE-101 Phase 1 Part B monotherapy sufficient to begin a Phase 2 clinical trial and (y) unrestricted and unencumbered net cash proceeds in a specified amount from the issuance and sale by the Company of its equity securities to investors acceptable to SVB (Filing, 8-K, Cue Biopharma, FEB 15, 2022, View Source [SID1234608316]).

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The SVB Term Loans bear interest at a floating rate per annum equal to the greater of (A) the prime rate (as published in the money rates section of The Wall Street Journal) plus 2.25% and (B) 5.50%. On the first calendar day of each month, the Company will be required to make monthly interest payments and commencing on June 30, 2023 (extended to December 31, 2023 if the tranche B term loans are advanced), the Company will be required to repay the SVB Term Loans in (i) 30 consecutive installments of principal plus monthly payments of accrued interest if the tranche B term loans are not advanced and (ii) 24 months if the tranche B term loans are advanced. All outstanding principal and accrued and unpaid interest under the SVB Term Loans and all other outstanding obligations with respect to the SVB Term Loans are due and payable in full on December 1, 2025.

The SVB Loan Agreement permits voluntary prepayment of all, but not less than all, of the SVB Term Loans, subject to a prepayment premium except if the facility is refinanced with another SVB facility. Such prepayment premium would be 3.00% of the principal amount of the SVB Term Loans if prepaid prior to the first anniversary of the Effective Date, 2.00% of the principal amount of the SVB Term Loan if prepaid on or after the first anniversary of the Effective Date but prior to the second anniversary of the Effective Date, and 1.00% of the principal amount of the SVB Term Loan if prepaid on or after the second anniversary of the Effective Date. Upon repayment in full of the SVB Term Loans, the Company will be required to pay a final payment fee equal to 5.00% of the original principal amount of any funded term loan being repaid.

The SVB Term Loans and related obligations under the SVB Loan Agreement are secured by substantially all of the Company’s properties, rights and assets, except for its intellectual property (which is subject to a negative pledge under the SVB Loan Agreement). The SVB Loan Agreement contains customary representations, warranties, events of default and covenants, including a requirement that the Company maintain in accounts of the Company at SVB unrestricted and unencumbered cash equal to the lesser of all of the Company’s cash and 110% of the obligations to SVB. The occurrence and continuation of an event of default could cause interest to be charged at the rate that is otherwise applicable plus 3.00% (unless SVB elects to impose a smaller increase) and would provide SVB with the right to accelerate all obligations under the SVB Loan Agreement and exercise remedies against the Company and the collateral securing the SVB Term Loan and other obligations under the SVB Loan Agreement, including foreclosure against assets securing the SVB Term Loan and other obligations under the SVB Loan Agreement, including the Company’s cash.