On April 13, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported that the Company has launched beLAB2122, a translational $ 20 million BRIDGE in collaboration with Bristol-Myers Squibb Company (NYSE: BMY) (Press release, Evotec, APR 13, 2021, View Source;announcements/p/evotec-launches-belab2122-translating-academic-innovation-from-leading-german-life-science-region-in-collaboration-with-bristol-myers-squibb-6047 [SID1234577948]). beLAB2122 brings together leading academic institutions from the Rhine-Main-Neckar region of Germany with the goal of efficiently advancing first-in-class therapeutic options across all therapeutic areas and formats into investable drug discovery and early development projects.

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LET’S CALL EVOTEC | THOMAS HANKE ON BELAB2122 AND BRIDGES

Mediated and supported by BioRN, the Life Science Cluster Rhein Neckar, beLAB2122 for the first time brings together the European Molecular Biology Laboratory ("EMBL"), the German Cancer Research Center ("DKFZ"), the Goethe University Frankfurt, Heidelberg University and the University of Tübingen in one collaboration with industry partners. Evotec’s BRIDGE (Biomedical Research, Innovation & Development Generation Efficiency) collaborations provide an integrated fund and award framework to validate exciting academic projects in collaborations with pharma and funders which may lead to the formation of jointly owned new companies. Since 2016, Evotec has established several BRIDGE collaborations with a variety of academic, pharma, and venture capital partners across Europe and North America.

Evotec launches beLAB2122 in cooperation with Bristol Myers Squibb, Evotec’s long-standing collaborator in drug discovery across several therapeutic areas. Together the sponsors intend to tap into Europe’s foremost academic clusters of excellence in the life sciences, both validating and advancing innovative research in therapeutics and related technologies from academia to enable the formation of new, collectively owned spin-out companies.

Dr Werner Lanthaler, Chief Executive Officer of Evotec, said: "We are very excited about the launch of beLAB2122, a truly transformative framework that leverages first-class science from one of Europe’s leading life science cluster regions with lots of potential to generate medical progress. We look forward to unlocking this potential by using our ‘data-driven R&D Autobahn to Cures’ to further validate and develop these approaches to translate the promising early-stage research into the medicines of the future."

Dr Thomas Hanke, Head of Academic Partnerships at Evotec, added: "We are delighted to see the first BRIDGE in Germany becoming reality and look forward to working closely with our academic partners in the Rhine-Main-Neckar area and our colleagues at Bristol Myers Squibb to identify and accelerate the next generation of first-in-class therapeutics across all modalities and therapeutic areas. We would also like to particularly thank BioRN for continuously supporting beLAB2122."

Dr Rupert Vessey, Executive Vice President and President, Research and Early Development at Bristol Myers Squibb commented: "We are excited by the opportunity to support beLAB2122 in the translation of novel scientific research from these leading German academic institutions. Given their past experience with successful BRIDGEs, we believe Evotec is well-equipped to interpret the many lines of scientific inquiry resulting from this collaboration and use its proprietary platforms to deliver quality data that may one day lead to potentially novel therapies for patients."

Prof. Matthias Hentze, EMBL Director, said: „This collaboration has been established at a time of increasing awareness that the efficient and rapid translation of research outcomes is essential. beLAB2122 is a transformative collaboration to accelerate the validation of therapeutic concepts for the benefit of society. EMBL, as Europe’s leading molecular biology research institute, is delighted to be part of this initiative along with some of the most renowned institutes in the region and beyond. With Evotec and Bristol Myers Squibb this collaboration has world-renowned industrial sponsors to help bring successful ideas into the market and to foster cutting-edge research and innovation."

Dr Rainer Wessel, Chief Innovation Officer, German Cancer Research Center (DKFZ), added: "For DKFZ, a major goal is to foster transfer of our excellent research into highly innovative applications that benefit cancer patients world wide. The beLAB2122 collaboration is a major step in gaining critical mass and speed together with other scientific and commercial leaders to achieve that goal."

Prof. Dr Manfred Schubert-Zsilavecz, Vice President of Goethe University Frankfurt responsible for the Third Mission and Professor for Medicinal Chemistry, pointed out: "Pharmaceutical and translational medical research are two of the key strengths of Goethe University Frankfurt, and numerous of our research projects aim to contribute to closing the innovation gap in drug development. We are extremely happy to be part of the beLAB2122 research network in order to boost cooperation between academic and industrial research, for the sake of suffering patients."

Prof. Dr Matthias Weidemüller, Vice-Rector Innovation and Transfer, Heidelberg University, affirmed: "Heidelberg University is excited to be part of the Evotec BRIDGE collaboration beLAB2122. It is of fundamental importance that our cutting-edge research be translated into applications on a broader scale. This collaboration brings together leading institutions in the Rhine-Main-Neckar region that conduct research at the forefront of life science. I am positive that – within the BRIDGE framework – we can generate added momentum for converting scientific achievements into future therapeutics."

Prof. Dr Peter Grathwohl, Vice-President of Research and Innovation of the University of Tübingen, joined: "The University of Tübingen is delighted to be part of beLAB2122. The transfer of research results to application is very important to us: In the future, we want to provide excellent opportunities for our researchers to contribute their expertise to concrete collaboration projects with sponsors in economy and industry."

The name beLAB2122 refers to the Rhine, Main, and Neckar rivers which connect the member institutions with one another and which total 2,122 kilometres in length. For further information on beLAB2122, please visit www.belab2122.org.

On April 12, 2021 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers, reported a clinical collaboration agreement with GlaxoSmithKline ("GSK") in which Zentalis will evaluate the combination of ZN-c3, Zentalis’ oral WEE1 inhibitor product candidate, and ZEJULA (niraparib), GSK’s poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with advanced epithelial ovarian cancer (Press release, Zentalis Pharmaceuticals, APR 12, 2021, View Source [SID1234643100]). Zentalis is currently conducting clinical studies with ZN-c3 both as a monotherapy and in combination with certain standard of care therapies.

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"This clinical collaboration and supply agreement with GSK allows us to investigate the broader potential of our WEE1 inhibitor when used as part of a combination treatment with niraparib, a PARP inhibitor," commented Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis Pharmaceuticals. "As demonstrated in our preclinical studies, ZN-c3 is designed to have significant advantages over other investigational WEE1 inhibitor therapies. We believe this combination has the potential to meaningfully improve the outcomes for patients with ovarian cancer."

PARP inhibitors prevent DNA damage repair in cancer cells. Similar to PARP, WEE1 plays a role in cellular regulation and repair, allowing cells with DNA damage to repair and survive. Inhibition of WEE1 causes dysregulation of DNA replication and subsequently induces apoptosis. Based on these complementary mechanisms of action, the use of WEE1 and PARP inhibitors could potentially have synergistic anti-tumor activity.

More than 300,000 women worldwide are diagnosed with ovarian cancer each year, leading to over 180,000 fatalities1. While substantial progress has been made in the treatment of this disease, there is an urgency to address the remaining unmet need through the development of innovative combination treatments.

Under the terms of the non-exclusive collaboration, Zentalis is responsible for conducting the study with GSK providing all required doses of niraparib. Zentalis maintains full ownership of ZN-c3.

1www.cancerresearch.org

About ZN-c3

ZN-c3 is an oral inhibitor of WEE1 in development for the treatment of advanced solid tumors. The inhibition of WEE1, a DNA damage response protein, aims to generate sufficient DNA damage in cancer cells, causing cell death, thereby preventing tumor growth and potentially causing tumor regression. Zentalis is currently conducting a Phase 1/2 clinical trial in patients with advanced solid tumors and reported initial data from the Phase 1 portion at the AACR (Free AACR Whitepaper) Annual Meeting 2021. In addition, the Company is also conducting a Phase 1b trial evaluating ZN-c3 in combination with chemotherapy in patients with advanced ovarian cancer, with plans to initiate a Phase 1/2 trial in combination with GSK’s niraparib in patients with advanced ovarian cancer, a Phase 1/2 trial in combination with chemotherapy in osteosarcoma and a Phase 2 trial investigating ZN-c3 as a monotherapy in patients with uterine serous carcinoma in 2021.

About ZEJULA (niraparib)

GSK’s ZEJULA (niraparib) is an FDA and EMA-approved oral, once-daily poly (ADP-ribose) polymerase inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies, including Phase III studies in ovarian and non-ovarian indications.

On April 12, 2021 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics, reported that the first patient has been dosed in the Phase 1 clinical trial of RTX-321 for the treatment of human papilloma virus (HPV) 16-postive cancers (Press release, Rubius Therapeutics, APR 12, 2021, View Source [SID1234584703]). RTX-321 is an allogeneic, off-the-shelf Red Cell Therapeutic product candidate that is engineered as an artificial antigen-presenting cell (aAPC) with a dual mechanism of action: boosting HPV 16-specific CD8+ T cell responses and promoting broad stimulation of both innate and adaptive immune responses. The Phase 1 clinical trial of RTX-321 is enrolling patients with persistent, recurrent, or metastatic, unresectable, HPV 16-positive cancers, including cervical cancer, head and neck squamous cell carcinoma (HNSCC) and anal cancer.

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"In preclinical studies, the surrogate model of RTX-321 induced a broad immune response and epitope spreading, suggesting that in patients, an effective immune response could be generated against multiple HPV antigens," said Christina Coughlin, M.D., Ph.D., chief medical officer of Rubius Therapeutics. "In patients, RTX-321 may also induce tumor-specific memory, potentially enabling the patient’s own immune system to remember a cancer’s identity, which could lead to long-term protection from tumor recurrence. Based on these findings, we believe that RTX-321 may lead to durable responses in patients with HPV 16-positive cancers."

RTX-321 expresses hundreds of thousands of copies of the costimulatory molecule 4-1BBL, the cytokine IL-12 and an HPV peptide antigen bound to major histocompatibility complex (MHC) class I proteins on the cell surface to mimic human T cell-APC interactions. As part of the manufacturing process, Rubius is producing frozen drug substance for the first time, enabling a truly off-the-shelf cellular therapy product candidate with a potential shelf life of up to several years.

"HPV 16 is the most common high-risk strain of HPV and is known to be associated with various types of cancer, including cervical cancer, head and neck squamous cell carcinoma and anal cancer. For patients with advanced HPV 16-positive cancers, the prognosis remains poor with few treatment options beyond the first-line setting," said Howard A. "Skip" Burris, III, M.D., president, clinical operations and chief medical officer, Sarah Cannon Research Institute. "RTX-321 offers a new potential option to treat these patients by utilizing the body’s own immune system. We look forward to working with Rubius Therapeutics to develop RTX-321 for the treatment of patients with HPV 16-positive cancers."

About HPV 16-Positive Cancers
Human papillomavirus (HPV) 16 is associated with approximately 70 percent of cervical cancers, approximately 40 percent of head and neck squamous cell carcinoma (HNSCC) arising in the oropharynx, approximately 25-40 percent of HNSCC arising in other locations and approximately 80-85 percent of anal cancers. A critical need remains for better treatment options for advanced HPV 16-associated cancers. The prognosis remains poor for patients with metastatic disease with few treatment options beyond the first-line setting.

About the RTX-321 Clinical Trial
Rubius Therapeutics is enrolling patients in a Phase 1 open-label, multicenter, monotherapy dose escalation, first-in-human study of RTX-321 for the treatment of patients that are HLA-A*02:01-positive with persistent, recurrent, or metastatic, unresectable, HPV 16-positive cancers, including unresectable cervical cancer (squamous, adeno, or adenosquamous histology), head and neck squamous cell carcinoma (including of the nasal and oral cavities, larynx, hypopharynx, nasopharynx, and oropharynx) and squamous cell cancer of the anal canal that is not amenable to curative therapy. The purpose of the trial is to determine the safety and tolerability, recommended phase 2 dose and pharmacology, and antitumor activity of RTX-321. For more information about the Phase 1 clinical trial of RTX-321, please visit clinicaltrials.gov (NCT04672980).

About RTX-321
RTX-321 is an allogeneic, off-the-shelf aAPC therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex (MHC) class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

On April 12, 2021 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported that clinical data from a compassionate use program for the treatment of metastatic melanoma at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual meeting April 10 – 15, 2021 (Press release, Instil Bio, APR 12, 2021, View Source [SID1234583990]). The presentation abstract and additional information is available on the AACR (Free AACR Whitepaper) conference web site at www.aacr.org.

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"Despite the recent advances in immunotherapy for solid tumors, many patients do not receive clinical benefit or experience relapse after an initial remission," said Robert Hawkins, MBBS FRCP, PhD, Chief Strategy Advisor to Instil and presenting study author. "In this compassionate use setting in which patients had exhausted all other available therapies, a one-time treatment with TILs was able to induce a remission in more than half of the treated patients."

"This presentation highlights the potential for ITIL-168 to produce deep and durable remissions in patients with advanced melanoma," said Bronson Crouch, Chief Executive Officer of Instil. "We eagerly anticipate beginning a global Phase 2 clinical trial investigating ITIL-168 for the treatment of advanced melanoma later this year."

In this compassionate use program, 21 patients with stage IV cutaneous melanoma were treated between 2011 and 2019 at the Christie Hospital in Manchester, United Kingdom with TILs manufactured by Instil. All TIL products were generated in Instil’s company-operated, in-house manufacturing facilities in Manchester.

Among the 21 patients, 14 (67%) achieved an objective response, with four (19%) achieving a complete response. All complete responders remained in remission at the time of data cutoff with those remissions ranging in duration from 30 months to over 80 months from TIL infusion. With a median duration of follow-up of 52.2 months, the median overall survival was 21.3 months with nearly half of patients experiencing long term survival. Side effects of treatment were largely transient, self-limited and generally attributable to the lymphodepleting chemotherapy regimen and post-TIL IL-2 treatment.

The company plans to submit these results for peer-reviewed publication in 2021.

Instil expects to begin a Phase 2 trial of ITIL-168 in advanced melanoma patients in the second half of 2021. The company anticipates obtaining topline safety and efficacy data in 2023, which could support the submission of a BLA to the FDA in 2023 and a Marketing Authorization Application to the European Medicines Agency in 2024.

Poster Information:

Title: Clinical Feasibility and Treatment Outcomes with Unselected Autologous Tumor Infiltrating Lymphocyte Therapy in Patients with Advanced Cutaneous Melanoma

Session Type: E-Poster Session

Session Title: Adoptive Cell Therapy

Abstract Number: LB150

About ITIL-168

ITIL-168 is an investigational, autologous cell therapy made from tumor infiltrating lymphocytes, or TILs. ITIL-168 is manufactured with Instil’s proprietary, optimized, and scalable manufacturing process, which has been designed to capture and preserve the maximum diversity of each patient’s TILs; the manufacturing process also offers significant scheduling flexibility for patients and physicians at the time of both tumor resection and TIL treatment. Instil plans to investigate ITIL-168 in a global phase 2 trial in advanced melanoma in 2021 and additional solid tumor indications in Phase 1 clinical trials beginning in 2022.

On April 12, 2021 Onxeo S.A. (Euronext Growth Paris: ALONX; Nasdaq First North Growth Copenhague: ONXEO, a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR), in particular against rare or resistant cancers, reported the result of its capital increase through the issuance of new shares (the "New Shares") with shareholders’ preferential subscription rights (PSR), whose subscription took place from March 19 to March 31, 2021 included in France and from March 19 to March 26, 2021 included in Denmark (Press release, Onxeo, APR 12, 2021, View Source [SID1234580416]).

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The gross amount of the capital increase, including the issue premium, amounted to 9.7 million euros and resulted in the creation of 13,677,125 New Shares, at a subscription price per share of 0.71 euro (5.287 DKK on the basis of an exchange rate of 7.447 DKK for 1 euro on March 9, 2021).

The proceeds from this issue of New Shares are intended to finance primarily the expansion and acceleration of the clinical development of AsiDNA, in particular in combination with other anti-cancer agents.

The Company also intends to:

continue the optimization and preclinical development of new candidates selected on the platON platform,
optimize pharmaceutical development and compound manufacturing operations, and
more generally, finance the Company’s operations.
Judith Greciet, CEO of Onxeo, said: "We would like to thank all our investors, both historical and new, who have contributed to the success of this fundraising. The renewed confidence in our long-term strategy by our two core shareholders, Financière de la Montagne and Invus, as well as by many other shareholders, secures the ramp-up of our development and extends our visibility until the end of 2022. With the funds raised, the Company will accelerate the development of AsiDNA with other clinical trials, notably in non-small cell lung cancer, with a phase 2 study designed to be extended as a potential pivotal trial. The clinical program should also include the United States as part of the acceleration plan. Additionally, we will expand our portfolio with other compounds from our platON platform."

The Board of Directors of Onxeo, in its meeting on April 12, 2021, recorded the amount of subscriptions and decided on the final terms of the capital increase with preferential subscription rights of shareholders decided on March 9, 2021.

RESULT OF THE RIGHT ISSUE

At the end of the subscription period, subscriptions totaled 13,677,125 shares, divided as follows:

6,111,797 New Shares were subscribed on an irreducible basis;
7,565,328 Shares News were requested on a free basis.
As the Company has decided to exercise the extension clause provided for in the 20th resolution of the General Meeting of June 19, 2020 for 4.8% of the initial offer, the new shares applied for on a free basis were fully allocated.

Consequently, the gross amount of the capital increase, including issue premium, amounts to 9,710,758.75 euros and results in the issue of 13,677,125 new shares, at a unit subscription price of 0.71 euros, corresponding to a subscription rate of approximately 104.8%.

The Company’s share capital following the capital increase will amount to 22,998,733.75 euros, divided into 91,994,935 shares with a par value of 0.25 euros each.

The settlement-delivery of the New Shares and their admission to trading on Euronext Growth Paris and Nasdaq First North Growth Copenhagen are scheduled for April 16 and April 19, 2021, respectively.

The New Shares will carry dividend rights and will be traded on the same quotation line as the existing shares (ISIN FR0010095596).

Impact of the issue on the shareholding structure

The following table presents the distribution of capital, to the Company’s knowledge, before and after the completion of the capital increase.

The commitments of the existing shareholders, Financière de la Montagne and Invus Public Equities LP, were fully subscribed for a total amount of 7 million euros, respectively 3 and 4 of which approximately 2.1 million euros were on an irreducible basis and 4.9 million euros on a free basis. The subscriptions of other investors thus amount to about 2.7 million euros.

Actionnaires Number of shares before the issue % of capital and voting rights(1) shares before the issue Number of shares after the issue % of capital and voting rights(1) shares after the issue
Financière de la Montagne 10,462,560 13.36% 14,708,767 15.99%
Invus Public Equities LP 8,397,270 10.72% 14,031,073 15.25%
Free float 59,457,980 75.92% 63,255,095 68.76%
Total 78,317,810 100.00% 91,994,935 100.00%
Theoretical voting rights. All shares have the same voting rights, with the exception of treasury shares held by the Company.
DILUTION

For information purposes, the impact of the issue on the capital ownership of a shareholder holding 1% of the Company’s share capital prior to the issue and who did not subscribe to the issue (calculations based on a number of 78,317,810 shares making up the Company’s share capital at December 31, 2020) is as follows:

Shareholder’s interest (%)
(en euro par action) Non-diluted basis Diluted basis (1)
Before issue of New Shares 1.00 0.95
After issue of 13,677,125 New Shares 0.85 0.81
(1) Taking into account the 4,335,740 options and warrants giving access to the share capital granted and outstanding as of today.

INDICATIVE TIMETABLE OF THE OPERATION

April 16, 2021 Issuance of New Shares – Settlement and Delivery.
April 19, 2021 Admission of the New Shares to trading on Euronext Growth Paris and Nasdaq First North Growth Copenhagen.

Contributors

– Invest Securities acted as Lead Manager and Bookrunner of the transaction.

– Invest Corporate Finance acted as Listing Sponsor.

– Nordea Denmark, a subsidiary of Nordea Bank Abp, Finland, acted as underwriting agent in Denmark.

AVAILABILITY OF THE PROSPECTUS

The Prospectus, having received the approval n°21-063 dated March 9, 2021 from the Autorité des marchés financiers ("AMF"), consists of (i) the Universal Registration Document of Onxeo filed with the AMF on April 27, 2020 under number D.20-0362 (the "Universal Registration Document"), (ii) the Amendment to the Universal Registration Document, filed with the AMF on March 9, 2021 under number D.20-0362-A01, (iii) a Securities Note and (iv) a summary of the Prospectus (included in the Securities note).

Copies of the Prospectus are available free of charge at the registered office of Onxeo, 49, boulevard du Général Martial Valin – 75015 Paris. The Prospectus may also be consulted on the websites of the AMF (www.amf-france.org) and Onxeo (www.onxeo.com) and from the Lead Manager and Bookrunner.

In connection with the opening of the public offering in Denmark, an unofficial translation into English of all the documents constituting the prospectus has also been prepared by the Company. In the event of any discrepancy between the French prospectus and the English translation, the French version will prevail. These documents are also available free of charge at Onxeo’s registered office at 49, boulevard du Général Martial Valin – 75015 Paris and on Onxeo’s website (www.onxeo.com).

Risk Factors

Investors are invited to carefully consider the risk factors detailed in section 3 of the Universal Registration Document, section 2 of the Amendment to the Universal Registration Document and section 2 of the Securities Note. The occurrence of all or part of these risks may have an adverse effect on the Group’s business, financial position, results or ability to achieve its objectives.