On April 18, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported the initiation of a Phase 2 study of the company’s lead drug candidate, STP705, for Keloid scar prevention (Press release, Sirnaomics, APR 18, 2021, View Source [SID1234578167]). The Phase 2, multi-center, randomized, double-blind, multiple-arm, controlled study is designed to evaluate the safety and efficacy of various doses of STP705 in reducing post-keloidectomy keloid recurrence.

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The primary endpoint of this trial is to measure the rate of recurrence in patients who have undergone surgery alone (receiving placebo) versus surgery and STP705 at three months, six months, and 12 months post-surgical excision.

"We anticipate that this important study should render additional data on STP705’s unique mechanism of action on skin fibrotic scarring, following the promising results in previous studies," said Patrick Lu, Ph.D., founder, President and CEO of Sirnaomics. "This approach for Keloid scar prevention is indicative of our strategy to leverage STP705’s dual-targeted inhibitory property and polypeptide nanoparticle-enhanced delivery to develop improved options for treating different cancer indications."

"Keloid scarring is a serious medical condition resulting in abnormal scar formation and pain along with having a very negative psychological impact on patients who suffer from the disease," said Michael Molyneaux M.D., Chief Medical Officer. "There is currently no treatment apart from surgical removal and this carries a very high recurrence rate. We seek to offer patients a viable alternative to prevent recurrence after surgical resection."

Sirnaomics expects to report initial clinical data from the Phase 2 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04844840.

About Keloid Scar
Keloids form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient’s quality of life, both physically and psychologically. Multiple studies on keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction.

Pathophysiology of keloids entails a prolonged inflammatory and proliferative phase of wound healing after injury. Among various cytokines promoting keloids formation, TGF-β1 is known as a key regulator of the aberrant fibrogenic response, while COX-2 acts a potent proinflammatory and proliferative mediator. When STP705 was locally injected into the human hypertrophic scar tissues, which were surgically removed from patients and implanted onto nude mice, the company observed scar size reductions, accompanying with not only target gene silencing but down regulation of fibrogenic markers including α-SMA, hydroxyproline, Collagen 1, and Collagen 3. Further analysis revealed that STP705 is able to induce fibroblast apoptosis both in vitro and in vivo. Therefore, the synergistic effect of simultaneous silencing of TGF-β1 and COX-2 may reverse skin fibrotic scarring through minimizing inflammation and activating fibroblast apoptosis. This mechanism of action of STP705 can be widely applied for treatment of many fibrotic conditions.

About STP705
Sirnaomics’ leading product candidate, STP705, is a siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the US FDA and Chinese NMPA, including treatments of cholangiocarcinoma, nonmelanoma skin cancer and hypertrophic scar. STP705 has also received Orphan Drug Designation for treatment of cholangiocarcinoma and primary sclerosing cholangitis. A Phase 2a study of STP705 for treatment of squamous cell skin cancer (isSCC) in adult patients demonstrated positive efficacy and safety results, with 76% of all patients (19/25) achieving complete histologically clearance and the two optimal dosing ranges achieving 90% histological clearance of tumor cell in the lesion. No significant or serious adverse events, including no significant cutaneous skin reactions, were reported in the study, and the company was able to define a clear therapeutic window in advance of later stage studies.

On April 18, 2021 Transcenta Holding Limited (Transcenta), a clinical stage global biotherapeutics company with fully-integrated capabilities in discovery, development and manufacturing of antibody-based therapeutics, reported the first patient has been successfully dosed in Phase I clinical study of TST001, a humanized monoclonal antibody targeting human Claudin18.2 (CLDN18.2), in combination with CAPOX for the treatment of patients with first-line locally advanced unresectable or metastatic gastric cancer (Press release, Transcenta, APR 18, 2021, View Source [SID1234578147]).

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TST001 is a second-generation recombinant humanized monoclonal antibody targeted CLDN18.2，generated by Transcenta’s independently-developed Immune Tolerance Breaking Technology (IMTB) platform. TST001 can target and kill tumor cells expressing CLDN18.2 by leveraging mechanisms such as complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) through combining CLDN18.2 with high specificity and affinity. With advanced technology, the fucose content of TST001 was significantly reduced during the production, which further enhancing the ADCC-mediated tumor killing activity of TST001. TST001 demonstrated better antitumor efficacy than IMAB362 analogues in pharmacodynamic experiments in mice (in vivo). TST001 has been launched in clinical research in China and US in July 2020 (NCT04396821, NCT04495296/CTR20201281).

"CLDN18.2 is found to be overexpressed in many tumors including gastric cancer，pancreatic cancer and esophageal cancer. At present, the first-in-class drug IMAB362 has shown promising efficacy in phase II FAST study mainly in first-line gastric cancer patients with high CLDN18.2 expression. "Professor Lin Shen from Beijing Cancer Hospital, believes that "Rapidly advancing the study of the combination of TST001 and standard chemotherapy in first-line gastric cancer patients could help us to accelerate the assessment of its therapeutic value in large number of gastric cancer patients expressing CLDN18.2."

"Gastric cancer is the most common tumor species in China and Asia. About 70% of gastric cancer patients express CLDN18.2. TST001 is a second-generation recombinant humanized monoclonal antibody targeted CLDN18.2. Preclinical studies have found that TST001 can not only efficiently kill gastric cancer cells with high expression of CLDN18.2, but also be very effective against gastric cancer cells with moderate to high expression of CLDN18.2. TST001 has been launched in clinical research in China and US in July 2020. We hope to explore the safe tolerance and anti-tumor activity of TST001 combined with CAPOX in first-line gastric cancer patients through this study, so as to provide a basis for later registrational clinical studies." said Dr. Michael Shi, EVP, Head of Global R&D and CMO of Transcenta.

On April 16, 2021 T-Cure Bioscience, Inc., a privately held company focused on developing T cell receptor (TCR) therapy products for the treatment of solid tumors, reported that management will present virtually at the following upcoming webinar and healthcare conference (Press release, T-Cure Bioscience, APR 16, 2021, View Source [SID1234580486]):

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Beacon Targeted Therapies’ Cell Therapies-Frontiers in Solid Tumor Treatment

Gang Zeng, Chief Executive Officer, will participate the fireside panel discussion on Tuesday, April 20, 2021 at 12:00 p.m. (EDT). Dr. Zeng will cover general topics of adoptive cell therapy, including opportunities to overcome current challenges in treating solid tumors.
TCR-based Therapies Summit

Erika von Euw, Senior Director of Translational Research, will lead a workshop on Tuesday, June 8, at 9:30 a.m. (EDT), titled "Development of Novel TCRs Derived from Responding Patients."
Gang Zeng, will give a presentation on Tuesday, June 8, at 3:00 p.m. (EDT), titled "Leveraging the Insights Gained from TIL Therapy to Improve Solid Tumor Immunotherapy".

On April 16, 2021 AstraZeneca reported that proposed acquisition of Alexion Pharmaceuticals, Inc (Alexion) has achieved an important step toward completion, having cleared US Federal Trade Commission review (Press release, AstraZeneca, APR 16, 2021, View Source [SID1234578146]). This follows the conclusion of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

The announcement follows competition clearances in Canada, Brazil, Russia and other countries globally, with a full list available on astrazeneca.com. Additional global regulatory clearances are pending, including but not limited to the UK, EU and Japan.

Marc Dunoyer, Executive Director and Chief Financial Officer, said: "These clearances further advance us towards closing our acquisition of Alexion. We remain focused on the next chapter for AstraZeneca and Alexion, building on our combined expertise in immunology and precision medicines and our shared ambition to bring more innovative medicines to patients worldwide. We look forward to working closely with other global authorities as we progress toward this goal."

The proposed acquisition, first announced in December 2020, would enhance the Company’s scientific presence in immunology by adding Alexion’s innovative complement-technology platforms and strong pipeline. Rare diseases represent a high-growth disease area with rapid innovation and significant unmet medical need. The acquisition remains expected to close in Q3 2021, subject to receipt of additional global regulatory clearances and approval by shareholders of both companies with shareholder voting anticipated on 11 May 2021.

Subject to a successful completion of the acquisition, a dedicated business unit will be created, known as ‘Alexion, The AstraZeneca Rare Disease Unit’, headquartered in Boston, US. AstraZeneca will have an enhanced global footprint and broad coverage across primary, speciality and highly specialised care, and is expected to deliver double-digit revenue growth through 2025, double-digit core EPS accretion for the first three years as well as strong cash flow with an ambition to increase the dividend.

Rare diseases
Over 7,000 rare diseases are known today, and only c.5% have US Food and Drug Administration-approved treatments.1 Demand in the global rare disease space is forecasted to grow by a low double-digit percentage in the future.2

Important additional information
In connection with AstraZeneca’s proposed acquisition of Alexion (the Acquisition), AstraZeneca filed a registration statement on Form F-4 (the Registration Statement), which has been declared effective by the United States Securities and Exchange Commission, and which includes a document that serves as a prospectus of AstraZeneca and a proxy statement of Alexion (the proxy statement/prospectus). Alexion filed the proxy statement/prospectus as a proxy statement and AstraZeneca filed the proxy statement/prospectus as a prospectus with the SEC on 12 April 2021, and each party will file other documents regarding the Acquisition with the SEC. Investors and security holders of Alexion are urged to carefully read the entire Registration Statement and proxy statement/prospectus and other relevant documents filed with the SEC when they become available, because they will contain important information. Investors and security holders may obtain the Registration Statement and the proxy statement/prospectus free of charge from the SEC’s website or from AstraZeneca or Alexion as described in the paragraphs below.

The documents filed by AstraZeneca with the SEC may be obtained free of charge at the SEC’s website at www.sec.gov. These documents may also be obtained free of charge on AstraZeneca’s website at View Source under the tab "Investors". The documents filed by Alexion with the SEC may be obtained free of charge at the SEC’s website at www.sec.gov. These documents may also be obtained free of charge on Alexion’s website at View Source under the tab, "Investors" and under the heading "SEC Filings" or by contacting Alexion’s Investor Relations Department at [email protected].

Participants in the solicitation
AstraZeneca, Alexion and certain of their directors, executive officers and employees may be deemed participants in the solicitation of proxies from Alexion shareholders in connection with the Acquisition. Information regarding the persons who may, under the rules of the SEC, be deemed participants in the solicitation of the shareholders of Alexion in connection with the Acquisition, including a description of their direct or indirect interests, by security holdings or otherwise, is set forth in the proxy statement/prospectus or proxy statement filed with the SEC on 12 April 2021. Information about the directors and executive officers of Alexion and their ownership of Alexion shares is set forth in Alexion’s Annual Report on Form 10-K/A, as previously filed with the SEC on 16 February 2021. Free copies of these documents may be obtained as described in the paragraphs above.

Important notices relating to financial advisors
Evercore Partners International LLP (Evercore), which is authorised and regulated by the FCA in the United Kingdom, is acting exclusively for AstraZeneca and no one else in connection with the Acquisition and the matters referred to in this announcement and will not regard any other person as a client in relation to the matters set out in this announcement (whether or not a recipient of this announcement) and will not be responsible to anyone other than AstraZeneca for providing the protections afforded to its clients, nor for providing advice in relation to the Acquisition or any other matter referred to in this announcement. Neither Evercore nor any of its subsidiaries, holding companies, branches or affiliates owes or accepts any duty, liability or responsibility whatsoever (whether direct or indirect, whether in contract, in tort, under statute or otherwise) to any person who is not a client in connection with the Acquisition or any statement contained in this announcement or otherwise. Apart from the responsibilities and liabilities, if any, which may be imposed on Evercore by the Financial Services and Markets Act 2000 (FSMA), or the regulatory regime established thereunder, or under the regulatory regime of any jurisdiction where exclusion of liability under the relevant regulatory regime would be illegal, void or unenforceable, neither Evercore nor any of its affiliates accepts any responsibility or liability whatsoever for the contents of this announcement, and no representation, express or implied, is made by it, or purported to be made on its behalf, in relation to the contents of this announcement, including their accuracy, fairness, sufficiency, completeness or verification of any statement contained in this announcement or any other statement made or purported to be made by it, or on its behalf, in connection with AstraZeneca or the matters described in announcement, and nothing in this announcement is, or shall be relied upon as, a promise or representation in this respect, whether as to the past or the future. To the fullest extent permitted by applicable law, each of Evercore and its affiliates accordingly disclaim all and any responsibility or liability whether arising in tort, contract or otherwise (save as referred to above) which they might otherwise have in respect of this announcement or any statement contained in this announcement.

Centerview Partners UK LLP (Centerview Partners), which is authorised and regulated by the FCA in the United Kingdom, is acting exclusively for AstraZeneca and no one else in connection with the Acquisition and the matters referred to in this announcement and will not regard any other person as a client in relation to the matters set out in this announcement (whether or not a recipient of this announcement) and will not be responsible to anyone other than AstraZeneca for providing the protections afforded to its clients, nor for providing advice in relation to the Acquisition or any other matter referred to in this announcement. Neither Centerview Partners nor any of its subsidiaries, holding companies, branches or affiliates owes or accepts any duty, liability or responsibility whatsoever (whether direct or indirect, whether in contract, in tort, under statute or otherwise) to any person who is not a client in connection with the Acquisition or any statement contained in this announcement or otherwise. Apart from the responsibilities and liabilities, if any, which may be imposed on Centerview Partners by the FSMA, or the regulatory regime established thereunder, or under the regulatory regime of any jurisdiction where exclusion of liability under the relevant regulatory regime would be illegal, void or unenforceable, neither Centerview Partners nor any of its affiliates accepts any responsibility or liability whatsoever for the contents of this announcement, and no representation, express or implied, is made by it, or purported to be made on its behalf, in relation to the contents of this announcement, including their accuracy, fairness, sufficiency, completeness or verification of any statement contained in this announcement or any other statement made or purported to be made by it, or on its behalf, in connection with AstraZeneca or the matters described in this announcement, and nothing in this announcement is, or shall be relied upon as, a promise or representation in this respect, whether as to the past or the future. To the fullest extent permitted by applicable law, each of Centerview Partners and its affiliates accordingly disclaim all and any responsibility or liability whether arising in tort, contract or otherwise (save as referred to above) which they might otherwise have in respect of this announcement or any statement contained in this announcement.

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On April 16, 2021 Oblique Therapeutics AB, a Sweden-based biotech company, reported that in collaboration with Karolinska Institutet (Stockholm, Sweden), Gothenburg University (Sweden) and several local biotechs published promising research results in the highly-acclaimed scientific journal Science Advances (AAAS) entitled: Rational Antibody design for Undruggable Targets using Kinetically Controlled Biomolecular probes (Press release, Oblique Therapeutics, APR 16, 2021, View Source [SID1234578145]). The peer-reviewed article describes how Oblique Therapeutics´ Abiprot technology can be used to discover and develop pharmacologically tailored antibodies against clinically important targets widely considered undruggable with antibodies. Two example antibodies are presented in the article. One is targeting hTRPV1, a clinically validated pain target. The second antibody is targeting KRAS, a highly relevant oncogene of critical importance in the etiology of many aggressive cancers (ex: pancreatic cancer). These early results have the potential to contribute to the development of much needed novel medicines across several therapeutic areas.

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The global antibody therapeutics market is estimated to be worth close to 200 Bn USD in 2026 (MarketWatch). Surprisingly, only about 60 antibody medicines (based on target), are currently available to patients. Important target classes such as G-protein-coupled receptors and ion channels are particularly underexploited. In contrast, there are about 1,500 known drug targets of which several are clinically or human-genetics validated. Novel medicines addressing these drug targets would bring game changing benefits to large populations of patients suffering from uncurable, untreatable, and refractory disease. A staggering example is the need for new pain medications to replace the unsatisfactory and addictive morphine and opioid regimens. But here, and in many other therapeutic areas, current antibody technologies fail to deliver meaningful medicines.

The research article in Science Advances presents a new high-tech antibody discovery approach called Abiprot, developed from nanoscience, computer technology, and proteomics. Abiprot identifies antibody binding sites on native-state, disease-relevant proteins at high resolution. The platform was developed by Oblique Therapeutics with the intention to create new antibody medicines addressing large unmet medical needs across several therapeutic areas. As an example, the paper demonstrates the first-ever stimuli-selective monoclonal antibody targeting TRPV1, prospectively developed for replacing opioids in pain management. Another example includes novel mutant-selective KRAS antibodies providing means to target the most prevalent KRAS mutated cancers.

Prof. Owe Orwar, CEO Oblique Therapeutics: "The excitement and joy of science and technological advancement is to prove that what was previously impossible or highly improbable is now possible. Even more satisfying is if the impossible or improbable translate into a hope for creating higher societal values, better health, and improved quality of life for millions of patients. Our dream is that the published technology will widen the scope of antibody therapeutics for the benefit of patients and we are very excited about what the future will hold. Science Advances, is globally ranked as the number three scientific journal in multidisciplinary sciences only after Nature (Springer Nature Limited) and Science (AAAS). To be able to publish company-critical results in Science Advances is therefore a testimony to the importance and potential impact of the study results. Since the conclusion of the published study, we have made significant advancements, and improvements in our antibody programs. For the TRPV1 antibody program we have entered into an R&D collaboration and exclusive option to licence agreement with a top-20 pharma company. A key component in our vision is to be the first-ever pharma company to bring a pain antibody medicine targeting ion channels to market".

Collaboration

The research was conducted by Oblique Therapeutics AB in collaboration with scientists from:

The Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
View Source

About Abiprot

Abiprot is a proprietary methodology to identify epitopes on protein targets that have previously proven difficult to address with antibodies. Abiprot can identify high-affinity antibody binding sites in a given protein with single amino acid resolution while the protein resides in its native environment. It is based on using a tailored molecular reporter system and proteomics. The platform yields detailed sequence and structure information for epitope identification and development. Oblique Therapeutics is applying this technology for discovery of a new generation of selective antibody therapeutics targeting cancer and pain.