On June 8, 2021 InflaRx N.V. (Nasdaq: IFRX), a clinical-stage biopharmaceutical company developing anti-inflammatory therapeutics by targeting the complement system, reported the enrollment of the first patient in an open-label, multicenter Phase II clinical study evaluating vilobelimab alone and in combination with pembrolizumab in patients with PD-1 or PD-L1 inhibitor resistant/refractory locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) (Press release, InflaRx, JUN 8, 2021, View Source [SID1234583715]).

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The Phase II clinical trial is expected to enroll approximately 70 patients at sites in Europe, the U.S. and elsewhere. The study will investigate two independent arms: vilobelimab alone and vilobelimab in combination with pembrolizumab. The main objectives of the trial are to assess the safety and antitumor activity of vilobelimab monotherapy and to determine the maximum tolerated or recommended dose, safety and antitumor activity in the combination arm.

Dr. Korinna Pilz, Global Head of Clinical Research and Development at InflaRx, said: "We are pleased to initiate the first clinical trial to evaluate vilobelimab in cancer. Scientific data suggest C5a involvement in tumor formation and progression, as well as in immunosuppression. Additionally, there is pre-clinical evidence of synergies between PD-1 and C5a/C5aR inhibitors in inducing anti-tumor responses. Based on this, we believe that vilobelimab has the potential alone and in combination with the PD-1 checkpoint inhibitor pembrolizumab to treat the advanced stages of this potentially deadly skin cancer."

The C5a/C5aR pathway has been implied as a potential driver for tumorigenesis, metastases and avoidance of immune cell destruction, particularly in the context of cSCC.

Several independent pre-clinical studies showed that the combination of a C5a or C5aR pathway inhibitor with inhibition of the PD-1/PD-L1 axis leads to an antitumoral effect, which was stronger than inhibition of one of the axes alone. This provides a pre-clinical rationale for the combined blockade of PD-1 and C5a to restore antitumor immune responses and to inhibit tumor cell growth.

About cutaneous squamous cell carcinoma (cSCC)

cSCC is the second most common form of skin cancer and, if caught early, it is generally curable. In the U.S. alone, according to the Skin Cancer Foundation, an estimated 1.8 million cases are diagnosed each year, which translates to about 205 cases diagnosed every hour. The incidence of cSCC has increased up to 200 percent in the past three decades. Over 15,000 people in the U.S. die each year from this disease. Approximately 5% of patients with cSCC develop locally advanced or metastatic disease. These forms of cSCC have a poor prognosis with low survival rates.

About vilobelimab (IFX-1):

Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. Vilobelimab has been demonstrated to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key "amplifier" of this response in pre-clinical studies. Vilobelimab is believed to be the first monoclonal anti-C5a antibody introduced into clinical development. Approximately 300 people have been treated with vilobelimab in clinical trials, and the antibody has been shown to be well tolerated. Vilobelimab is currently being developed for various indications, including Hidradenitis Suppurativa, ANCA-associated vasculitis, Pyoderma Gangraenosum and COVID-19 pneumonia.

On June 8, 2021 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Bemcentinib in combination with an anti-PD-(L)1 agent for the treatment of patients with AXL-positive advanced/metastatic non-small cell lung cancer (NSCLC) (Press release, BerGenBio, JUN 8, 2021, View Source;anti-pd-l1-combination-in-nsclc-301307422.html [SID1234583732]).

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The FDA’s decision represents the first recognition by a regulator of AXL-positive patients as a molecular targetable patient population. This designation has been granted for patients without actionable mutations, with disease progression on or after treatment with an anti-PD-(L)-1 agent, with or without chemotherapy as their first line of therapy.

Fast Track designation is intended to facilitate the development and review of drugs used to treat serious conditions and to fill an unmet medical need. It will enable BerGenBio to have more frequent interactions with the FDA throughout the drug development process, so that an approved product can reach the market faster.

The designation also provides Eligibility for Accelerated Approval, enabling approval based on a surrogate clinical endpoint; Priority Review, which allows New Drug Application (NDA) review in six months instead of 10, if relevant criteria are met; and eligibility for Rolling Review, whereby the Company will be able to submit completed sections of its NDA for review by the FDA before complete application is submitted.

BerGenBio has developed proprietary biomarkers and companion diagnostic assays for selection of AXL positive patients, the cAXL assay is validated for clinical trial use. Retrospective analysis of patients in clinical trials suggest approximately 50% of patients are cAXL positive, and it is these patients that achieve the clinical responses and extended survival benefit previously reported.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Building on our encouraging clinical and translational data, we are excited to receive Fast Track designation from the FDA for the promising combination of bemcentinib in combination with a checkpoint inhibitor. This regulatory milestone is particularly meaningful for BerGenBio, as it represents the first formal recognition by a regulator of AXL-positive patients as a discernible patient population and serves as further validation of our belief that AXL inhibition has high potential as a cornerstone of cancer combination therapy. We look forward to working closely with the FDA on the continued clinical development of the combination."

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the SARS-CoV-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment. Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response. Data from a Phase II in human clinical trial has shown that treatment with AXL inhibitor bemcentinib increased the rate ventilator free survival in hospitalised COVID-19 patients.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis

Composite AXL (cAXL) is a proprietary biomarker developed by BerGenBio that simultaneously scores AXL expression on tumour cells and immune cells in the tumour microenvironment, as determined by Immune Histo Chemistry (IHC) assay. Data from on-going clinical trials suggest ca. 50% of patients are high cAXL and this is predictive of improved clinical outcomes for patients receiving bemcentinib.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.

On June 8, 2021 Redx Pharma reported that H121 results highlight continued momentum and delivery against expectations, despite COVID headwinds on clinical studies (Press release, Redx Pharma, JUN 8, 2021, View Source [SID1234583899]). The start of the Phase I study of RXC007, a ROCK2 inhibitor for fibrosis, means the company now has two distinctly different in-house assets in the clinic. Lead in-house programme RXC004, a porcupine inhibitor for genetically selected solid tumours, is completing Phase I studies and set to enter Phase II trials during H221. The solid cash position of £39.9m supports increased R&D investment through to end-2022, covering several important value inflection points. Our updated rNPV-based valuation is £350.7m, equivalent to 128p/share (86p fully diluted).

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A second in-house programme enters the clinic Redx Pharma’s acknowledged expertise in medicinal chemistry underpins its discovery platform, and its strategy to develop best-or first-in-class small molecules that address validated biological targets in oncology and fibrosis indications. Two in-house programmes are now in clinical development: RXC004, a porcupine inhibitor for genetically selected solid tumours, is completing Phase I (both monotherapy and a PD-1 inhibitor combo) and set to enter Phase II studies; while RXC007, a ROCK2 inhibitor initially in development for fibrosis, dosed the first patient in its Phase I trial earlier in June.

▪ Funded through to value inflection points Redx Pharma has a solid balance sheet with £39.9m in cash resources. Funds are earmarked to progress RXC004 and RXC007 into Phase II proof-of-concept studies. RXC004 could, COVID permitting, post Phase II monotherapy results for MSS mCRC (microsatellite stable metastatic colorectal cancer) and biliary cancer in CY22 with interim monotherapy pancreatic cancer and MSS mCRC combination data also possible. For RXC007 the Phase I safety data should be available in H122, enabling a swift start to Phase II trials during H222. Our forecasts suggest the cash runway extends to end-2022.

▪ Building a track record of delivery The value of Redx Pharma’s medicinal chemistry expertise is being harnessed with a focussed, yet ambitious, strategy. The pipeline has been de-risked through preclinical outlicensing deals, with Jazz Pharmaceuticals and AstraZeneca, whilst retaining material commercial upside. However, it is the continued progress with its innovative in-house programmes that should, if successful, be transformative for the business over the medium term.

▪ rNPV valuation of £350.7m (128p/share) We value Redx Pharma using an rNPV and SOTP methodology, with conservative assumptions. Our updated model reflects recent clinical progress and generates a £350.7m valuation, or 128p/share (86p fully diluted) vs £326.4m, or 119p/share (84p, fully diluted) previously. Update 8 June 2021 Price 66.0p Market Cap £180.8m Enterprise Value £140.9m Shares in issue 273.9m 12 month range 11.7-95.0p Free float 11.0% Primary exchange AIM London Other exchanges N/A Sector Healthcare Company Code REDX Corporate client Yes Company description Redx Pharma specialises in the discovery and early clinical development of small molecule therapeutics, with an emphasis on oncology and fibrotic disease. Typically, these are progressed through proof-of-concept studies and then partnered for further development. The strategy has been validated by several collaborations.

Redx Pharma Redx Pharma: delivering on all key objectives The key message from Redx Pharma’s H121 results is the continued delivery of management against our, and the market’s, expectations. The recently announced start of a Phase I study with RXC007, a selective ROCK2 inhibitor, means that the company now has two in-house programmes in clinical development. The lead asset, porcupine inhibitor RXC004, is completing the fifth and final cohort (3.0mg) of the Phase I dose escalation study with results expected during H221. In addition, a Phase I study of RXC004 in combination with nivolumab (Bristol Myers Squibb’s PD-1 checkpoint inhibitor Opdivo), is underway with preliminary data expected in late-H221. Several RXC004 Phase II trials, in various oncology indications, are expected to start during H221.

Redx Pharma is well funded, with ample resources to achieve multiple value inflection points. Development progress with the lead assets during H121 lifted R&D investment to £10.3m (H120: £3.2m), similarly increasing operating costs from £5.2m to £12.6m. R&D spend is set to increase further as the clinical programmes progress, with the forecast cash runway extending through 2022. The cash balance of £39.9m at end-March 2021 was a sizeable improvement on the £1.9m figure a year earlier, reflecting the company’s refinancing in summer 2020 and its most recent successful £25.7m (gross) fund raise in December 2020. During H121, £5.1m of the £22.2m outstanding loan note held by majority shareholder Redmile Group was converted into equity. The 2020 raises added specialist investors Redmile, Sofinnova Partners, and Polar Capital to the shareholder register. The involvement of these respected and supportive investors provides valuable external validation of management’s clearly defined strategy.

Acknowledged medicinal chemistry expertise
Redx Pharma is focused on developing innovative small molecule pharmaceuticals, with the aim of creating best-or first-in-class compounds. Its medicinal chemistry expertise underpins the discovery platform, which has a growing industry-wide reputation and a proven ability to generate clinically, and commercially, attractive products. Management is actively addressing complex biological pathways, for instance the Wnt/β-catenin pathway, where its insights have resulted in generating novel small molecules such as its family of porcupine inhibitors (eg RXC004 and RXC006, partnered with AstraZeneca).

On June 8, 2021 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, reported that Alpine is set to join the broad-market Russell 3000 Index at the conclusion of the 2021 Russell indexes annual reconstitution, effective after the US market opens on June 28, 2021, according to a preliminary list of additions posted by FTSE Russell on June 4, 2021 (Press release, Alpine Immune Sciences, JUN 8, 2021, View Source [SID1234583700]).

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Annual Russell indexes reconstitution captures the 4,000 largest US stocks as of May 7, ranking them by total market capitalization. Membership in the US all-cap Russell 3000 Index, which remains in place for one year, means automatic inclusion in the small-cap Russell 2000 Index as well as the appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes.

For more information on the Russell 3000 Index and the Russell indexes reconstitution, go to the "Russell Reconstitution" section on the FTSE Russell website.

On June 8, 2021 Orion Corporation and the Finnish Red Cross Blood Service reported that they have concluded an agreement on research collaboration with the aim of developing chimeric antigen receptor (CAR) T-cell therapy (Press release, Orion , JUN 8, 2021, View Source [SID1234583716]).

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Cancer immunotherapies, with CAR T-cell therapy as one form of therapy, have introduced entirely new possibilities for cancer treatment. In CAR T-cell therapy, the patient’s own white blood cells are genetically modified to attack the cancer and kill it. CAR T-cells are currently used to treat certain haematological cancers.

The first T-cell therapies received marketing authorisation in the USA in 2017 and in Finland in 2019 for the treatment of recurrent acute lymphocytic leukaemia and B-cell lymphoma. Despite the good treatment results, development needs have been identified in CAR T-cell therapies, which is why research related to CAR-T cell therapy is being pursued.

The Blood Service has considerable experience in cell research, in the supply of cord blood and stem cell grafts classified as tissue products, and in the preparation of ATMP cell products classified as medicinal products. The Blood Service also has expertise and the necessary clean rooms for the research and high-quality production of therapeutic cells.

Orion has a solid research infrastructure and has introduced several proprietary drugs to the market in different therapy areas. Orion’s oncology therapy area researches and develops novel proprietary drugs for the treatment of cancer. In recent years, Orion has expanded its research activities to include immuno-oncology therapies.

New possibilities for cancer treatment

The research collaboration is based on new innovations to improve the structure of the CAR T-cell product. Matti Korhonen, Senior Medical Officer, who leads the research at the Blood Service, believes that the collaboration offers a great opportunity to develop new cell therapy products for patient care. According to Oliver Cooper, Ph.D., director of Discovery Sciences at Orion’s R&D, Orion’s drug development expertise will provide the necessary momentum for this project.

"Targeted immunotherapy has opened up entirely new possibilities for the treatment of cancer, and it is important to advance this development in Finland, too. I also believe that as a result of the development work, more and more patients will be able to benefit from this effective treatment," says Matti Korhonen

Project managers Satu Juhila from Orion and Jan Koski from the Blood Service say that the collaboration has got off to a good start: "Both parties are very enthusiastic regarding the opportunities of the collaboration and about advancing the development of cell therapy in Finland. We believe that the collaboration will provide plenty of new opportunities for the development of cell therapy products."