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.

On April 10, 2021 Tallac Therapeutics, Inc., a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported the first presentation of preclinical data demonstrating potent single-agent anti-tumor activity in preclinical cancer models with systemically administered TAC-001, the company’s lead clinical candidate from its novel Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform (Press release, Tallac Therapeutics, APR 10, 2021, View Source [SID1234579743]). The data will be presented today as part of the Immunomodulatory Agents and Interventions Session at Week I of the American Association of Cancer Research’s (AACR) (Free AACR Whitepaper) 2021 Virtual Annual Meeting (#AACR21) taking place April 10-15, 2021.

Toll-like receptor (TLR) agonists are a novel class of immunotherapy that generate both an innate and
adaptive immune response which may produce more robust and durable anti-cancer immunity to help
overcome resistance to standard-of-care oncology treatments. TLR9 is a key intracellular TLR present in
broad immune cell populations such as B lymphocytes and myeloid cells. Recent studies have shown that
the likelihood of patients responding to immune checkpoint inhibitor therapy may depend on B cells in
the tumor.i B cells play pivotal roles in the immune defense system, which bridge the innate and the
adaptive immunities against cancers.ii In preclinical studies, the activation of TLR9 in human and mouse
models drives B cell proliferation and differentiation.iii

"The results presented today at AACR (Free AACR Whitepaper) elucidate the unique properties of TAC-001 responsible for
integrating B cells and TLR9 activation which trigger innate and adaptive immune responses to create
potent, systemically delivered anti-tumor immunity across solid tumor types," said Dr. Hong I. Wan,
president, CEO and co-founder of Tallac Therapeutics. "The emerging data on TAC-001 continues to
strengthen our understanding of the roles that B cells and TLR9 activation play in eliciting anti-tumor
immunity in checkpoint inhibitor resistant and refractory settings and will help guide our clinical
development strategy."

In the e-poster, titled "TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells,
promotes anti-tumor immunity and favorable safety profile following systemic administration in
preclinical models," investigators present data providing evidence that in vitro targeted delivery of TAC001 leads to superior TLR9 activation in B cells, increased expression of co-stimulatory molecules and
cross-presentation leading to T cell proliferation. In vivo, TAC-001 demonstrated robust, curative and
durable single agent anti-tumor activity in checkpoint inhibitor resistant and refractory tumor models.
Additionally, the systemic administration of TAC-001 was shown to trigger both innate and adaptive
immunity by increasing B cell infiltration, T effector cell functions and modulation in suppressive myeloid
cells within the tumor microenvironment. These results support the development of TAC-001 for a broad
range of solid tumor malignancies.

AACR Poster Presentation Details:

Title: TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells, promotes antitumor immunity and favorable safety profile following systemic administration in preclinical models
Session Type: E-Poster Session
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions
Track: Immunology, Clinical Research Excluding Trials
Permanent Abstract Number: 1721
About TAC-001
TAC-001 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a potent Toll-like
Receptor 9 agonist (T-CpG) conjugated to an anti-CD22 antibody, a receptor restricted to B cells.
TAC-001 is designed to systemically deliver T-CpG to B cells by binding to CD22, leading to internalization
of TAC-001, TLR9 signaling, B cell activation and a cascade of immune reactions. Preclinical studies
demonstrate that the innate and adaptive immune responses triggered by TAC-001 leads to potent antitumor activity. TAC-001 is being developed to systemically deliver targeted immune activation in solid
tumor cancers.

On April 12, 2021 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX-V:BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company specializing in targeted immunotherapies for advanced breast cancer, reported the presentation of results from clinical studies with its lead product candidate, Bria-IMT, summarized in a poster session held at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, a virtual meeting, held over two weeks (Week 1: April 10-15; Week 2: May 17-21) (Press release, BriaCell Therapeutics, APR 12, 2021, View Source [SID1234578327]).

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The findings indicate disease control in advanced breast cancer patients, including stable disease (SD), partial responses (PR) or complete responses (CR). Disease control was especially noted in patients with Grade I/II (i.e. well or moderately differentiated) tumors or those that matched Bria-IMT at 2 or more HLA alleles. Patients with low or undetectable levels of circulating cancer cells were more likely to benefit from therapy.

Patients were treated with the Bria-IMT regimen alone (i.e. monotherapy study) or the Bria-IMT regimen in combination with immune checkpoint inhibitors, including pembrolizumab (KEYTRUDA; manufactured by Merck & Co., Inc.), and, more recently, Incyte’s retifanlimab (INCMGA00012, under a corporate collaboration with Incyte Corporation). Dr. Bill Williams, BriaCell’s President & CEO, presented the results of the clinical and pathological analysis. The patient data summarized and discussed belong to previously disclosed patients (i.e., no incremental numbers enrolled).

Details and results on the poster presentation are summarized below:

Poster Title: Predictors of response to a modified whole tumor cell immunotherapy in patients with advanced breast cancer from two phase I/IIa trials

Analysis and Discussion:

• The Bria-IMT regimen with or without checkpoint inhibitors is able to induce an effective immune response and disease control in heavily pre-treated advanced breast cancer patients. The patients were all heavily pretreated and failed multiple prior regimens.
• Delayed Type Hypersensitivity (DTH) to Bria-IMT analysis identified a group with significantly higher rates of disease control and progression-free survival (8 months) in both monotherapy and combination therapy studies suggesting a robust immune response is predictive of clinical benefit in these patients.
• Highest levels of disease control and PFS was observed in patients who matched Bria-IMT at 2 or more HLA alleles in the monotherapy study but not in the combination therapy study supporting our strategy to develop Bria-OTS, an off-the-shelf personalized immunotherapy for advanced breast cancer.
• Patients with Grade I/II tumors (median of 8 prior therapy regimens) were more likely to respond with disease control (67%) and longer progression free survival. The response was more pronounced in the patients in the combination therapy study suggesting additive or synergistic effects of checkpoint inhibitors when combined with the Bria-IMT regimen. Bria-IMT, with a molecular signature most closely related to Grade I/II tumors, may result in disease control and clinical benefit especially in this subset of patients.

A copy of the poster is posted at the following: View Source