On August 10, 2022 Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company with a Research & Development ("R&D") innovation engine that aims to discover, develop, and ultimately deliver impactful medicines to patients, reported financial results and business highlights for the second quarter ended June 30, 2022, and provided a program update for ZF874 for Alpha-1 Antitrypsin Deficiency (AATD) (Press release, Centessa Pharmaceuticals, AUG 10, 2022, View Source [SID1234618007]).

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"We continue to rapidly advance our robust rare diseases and immuno-oncology pipeline and set the stage for a number of important company milestones which we believe will help us address the needs of several patient populations," said Saurabh Saha, MD, PhD, Chief Executive Officer of Centessa. "We remain on track to initiate registrational studies for SerpinPC for the treatment of Hemophilia B in the second half of this year and look forward to initiating clinical trials with LB101 (PD-L1xCD47) for solid tumors, after our planned IND filing late this year. Beyond these, we are continuing to advance our earlier stage programs and expect multiple clinical proof of concept readouts across our pipeline over the next two years. Importantly, with a world-class R&D team and cash runway that extends into 2026, we are exceptionally well positioned to deliver on these goals."

ZF874 Program Update
The Company reported its decision to discontinue development of ZF874 following a recent report of an adverse event (AE) involving elevated liver enzymes (AST/ALT) in a PiMZ subject dosed with 5 mg/kg BID of ZF874 in the Phase 1 study. ZF874, a pharmacological chaperone designed to rescue the folding of the Z variant of alpha-1-antitrypsin (A1AT), was in a Phase 1 study for the treatment of AATD. As previously reported in November 2021, elevated liver enzymes were observed in a subject dosed with 15 mg/kg BID of ZF874 in the first cohort of patients within Part B of the Phase 1 study. Based on the results observed to date, the Company concluded that ZF874 was unlikely to achieve the desired target product profile.

Dr. Saha concluded, "While this is disappointing news for the A1AT patient community, we continue to believe that the pharmacological chaperone approach has the potential to address both the lung and liver manifestations of AATD. We are analyzing data from the Phase 1 study to help inform potential future development plans for our back-up compounds."

Recent Highlights

In July, the Company appointed Dr. Mathias Hukkelhoven, former Senior Vice President, Global Regulatory, Safety & Biometrics at Bristol Myers Squibb (BMS), to its Board of Directors. The Company also announced the addition of Dr. Harris L. Rotman as Senior Vice President of Regulatory Affairs.
In June, the Company presented the first preclinical data for LB101 (PD-L1xCD47) showing that single-agent LB101 delivered systemically led to meaningful tumor regressions and was well tolerated. The Company expects to initiate clinical trials with LB101 following its planned Investigational New Drug (IND) application submission late this year. Additional LockBody molecules, such as LB201 (PD-L1xCD3), are being progressed toward candidate selection expected early 2023.
Anticipated Upcoming Program Milestones

2H 2022: SerpinPC – Initiate registrational studies in Hemophilia B.
Q4 2022: SerpinPC – Two-year follow-up data from Phase2a open label extension study.
Q4 2022: LB101 – IND submission late this year.
The Company continues to progress its earlier stage programs and where applicable, expects to provide updates as they enter clinical studies.

Second Quarter 2022 Financial Results

Cash and Cash Equivalents: $484.2 million as of June 30, 2022, which the Company expects will fund operations into 2026, without drawing on the remaining available tranches under the Oberland credit facility.
Research & Development Expenses: $53.7 million for the quarter ended June 30, 2022, compared to $18.1 million for the quarter ended June 30, 2021.
General & Administrative Expenses: $14.8 million for the quarter ended June 30, 2022, compared to $11.8 million the quarter ended June 30, 2021.
Net Loss Attributable to Ordinary Shareholders: $64.7 million for the quarter ended June 30, 2022, compared to $41.5 million for the quarter ended June 30, 2021.

On August 10, 2022 Kuraray reported that Business Results for the Second Quarter of the Fiscal Year Ending December 31, 2022 (Press release, Kuraray, AUG 10, 2022, https://pdf.irpocket.com/C3405/BUJq/W42i/xImA.pdf [SID1234617993])

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1. Consolidated Financial Results for the Second Quarter of the Fiscal Year Ending December 31, 2022 (January 1, 2022 to June 30, 2022)
(1) Consolidated Operating Results (Percentage changes displayed for net sales, operating income, ordinary income and net income attributable to owners of the parent are comparisons with the corresponding period of the previous fiscal year.)
(2) Consolidated Financial Position

2. Dividends

3. Forecasts of Consolidated Financial Results for the Fiscal Year Ending December 31, 2022 (January 1, 2022 to December 31, 2022) (Percentage changes displayed for net sales, operating income, ordinary income and net income attributable to owners of the parent are comparisons with the previous fiscal year.)

On August 10, 2022 Artios Pharma Limited (Artios), a clinical stage biotech company pioneering the development of novel small molecule therapeutics that target the DNA damage response ("DDR") process in order to treat patients with a broad range of cancers, reported it has initiated a Phase 2 study with ART4215, a small molecule inhibitor of polymerase theta (Polθ) in combination with talazoparib (TALZENNA), an oral poly (ADP-ribose) polymerase (PARP) inhibitor in an expansion study for the treatment of BRCA deficient breast cancer (Press release, Artios Pharma, AUG 10, 2022, View Source [SID1234617987]).

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ART4215 is the first selective, oral, small molecule inhibitor of the Polθ polymerase domain to enter the clinic. Polθ, a DNA polymerase, is a tumor-specific DDR target involved in microhomology mediated end joining (MMEJ) that is overexpressed in many tumors and found in low levels in healthy tissue. Extensive preclinical studies have demonstrated that ART4215 has broad potential clinical utility, as described in Artios’ recent Nature Communications publication, Zatreanu et al., 2021. The Polθ project was originally in-licensed from Cancer Research Technology (now Cancer Research Horizons) in 2016 as part of the initial formation of Artios.

Dr. Niall Martin, Chief Executive Officer at Artios, said: "Polθ is highly expressed in cancer cells, but has limited expression in healthy cells, making it an attractive cancer target. Initial Phase 1 data supports a favorable tolerability profile and the potential for broad treatment use, particularly in combination with agents like PARP inhibitors where combinations with other DNA damage response inhibitors have been limited by toxicity. We are highly encouraged that ART4215 may offer a new treatment option that can synergize to overcome both de novo and acquired PARP resistance. We look forward to reporting Phase 1 safety and tolerability data in the first half of 2023."

Principal Investigator for the trial, Dr. Erika P. Hamilton, Director of the Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, said: "Patients with advanced solid tumors have achieved improved outcomes with the development of PARP inhibitors. However, there is still a need to address resistance mechanisms diminishing initial tumor responses and leading to disease progression. ART4215 has the potential to help overcome these limitations, and we are excited that the initiation of this Phase 2 trial represents an important step in the clinical evaluation of Polθ as a novel target."

ART4215 is currently being evaluated in an ongoing, first-in-human, global, open-label Phase 1/2 study to assess the safety, tolerability, pharmacokinetics, and clinical activity of ART4215 as a monotherapy or in combination with talazoparib in patients with advanced or metastatic solid tumors. Initial safety data from the first Phase 1 dose cohorts have demonstrated ART4215 to be well tolerated. A recommended Phase 2 dose has been established for ART4215 in combination with talazoparib, and a randomized expansion cohort has been initiated to evaluate the combination in patients with BRCA deficient breast cancer.

The study will enroll up to 206 patients and will be conducted at multiple oncology centers across the USA and Europe. The trial is led by principal investigators Erika P. Hamilton, M.D., Director of the Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, and Timothy Yap, M.B.B.S., Ph.D., Associate Professor of Investigational Cancer Therapeutics and Medical Director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center. Phase 1 safety and tolerability data is expected in the first half of 2023.

On August 10, 2022 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) and Alpine Immune Sciences, Inc. (NASDAQ: ALPN) reported that Evotec’s Seattle-based subsidiary, Just – Evotec Biologics, Inc., expanded a multi-year partnership with Alpine for the development of a commercial process for ALPN-303, an engineered TACI domain with significantly improved potency against the B cell cytokines BAFF and APRIL, being developed for the treatment of systemic lupus erythematosus and other B cell-mediated inflammatory and autoimmune diseases (Press release, Alpine Immune Sciences, AUG 10, 2022, View Source [SID1234617986]). The contract is a continuation of their first-in-human program initiated in 2020 in which Just – Evotec Biologics delivered drug substance materials using their J.DESIGN continuous manufacturing platform for Alpine’s ongoing Phase I study and anticipated Phase II studies of ALPN-303.

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This press release features multimedia. View the full release here: View Source

Under the expanded contract, Just – Evotec Biologics will leverage its data-driven technology platform to develop a commercial manufacturing process for ALPN-303. The program includes upstream and downstream process, analytical method, and formulation development with a view to support commercial manufacturing of ALPN‑303. Commercial process development activities will be performed at Just – Evotec Biologics’ state-of-the art J.POD biomanufacturing facility located in Redmond, Washington.

J.DESIGN, Just – Evotec Biologics’ data-driven, highly automated end-to-end biologics technology platform, employs a series of innovative technologies relying on the use of artificial intelligence, machine learning, intensified and continuous bioprocesses specifically designed for flexible and efficient biologics development, from discovery through to clinical and commercial manufacturing. The advanced Just – Evotec Biologics platform is specifically well suited for monoclonal antibodies and related protein modalities such as Fc fusion proteins. The J.POD facility was designed to support both clinical and commercial manufacturing processes while leveraging its expandable and highly flexible capacity.

Dr Linda Zuckerman, Executive Vice President, Global Head Biotherapeutics at Just – Evotec Biologics, commented: "We are excited to continue our highly collaborative partnership with the innovative team at Alpine to support the development of a commercial process for ALPN-303 in our state-of-the-art J.POD site in Redmond, WA."

Dr Craig Johnstone, Chief Operating Officer at Evotec, added: "We are proud to support Alpine in its endeavor to further develop ALPN-303. The combination of flexible manufacturing capacity with smart, robust and high-yielding process development makes Just – Evotec Biologics’ J.DESIGN the ideal platform to bring ALPN-303 to patients with currently significant unmet medical needs."

Dr Wayne Gombotz, Alpine’s Chief Technology Officer, commented: "ALPN-303 is a highly differentiated and promising therapeutic candidate with the potential to treat challenging target diseases such as lupus and other B-cell related inflammatory diseases. We are excited to be leveraging Just – Evotec Biologic’s J.DESIGN platform to bring this important therapeutic to late-stage clinical development."

About ALPN-303

ALPN-303 is a dual B cell cytokine antagonist being developed for multiple autoimmune and/or inflammatory diseases. Engineered by directed evolution, ALPN-303 potently inhibits the pleiotropic B cell cytokines B cell activating factor/B lymphocyte stimulator (BAFF, BLyS) and a proliferation inducing ligand (APRIL), which play key roles in B cell development, differentiation, and survival, and together contribute to the pathogenesis of multiple autoimmune diseases like systemic lupus erythematosus (SLE) and many other autoantibody-related inflammatory diseases. By simultaneously blocking these two cytokines, ALPN-303 has the potential to improve outcomes in patients suffering from severe autoimmune and/or inflammatory diseases.

On August 10, 2022 Australian biotechnology company Starpharma reported it has signed a new DEP Research Agreement with MSD, the trade name of Merck Sharp & Dohme LLC, Rahway, NJ, USA (Press release, Starpharma, AUG 10, 2022, View Source [SID1234617967]).

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This new DEP program will generate and evaluate additional DEP Antibody Drug Conjugates (ADCs).

This new agreement follows an earlier DEP Antibody Drug Conjugate (ADC) agreement that Starpharma signed with MSD in February 2021 as well as an expanded DEP Research Agreement with another large US biopharmaceutical company in June 2022.

"We are very pleased to add this new DEP ADC program with MSD and to continue building on our partnership with them in such an innovative and valuable area. This new DEP program underlines the potential clinical and commercial value our DEP technology can deliver," said Dr Jackie Fairley, CEO of Starpharma.

"This is the second DEP partnering agreement that Starpharma has signed in the last two months, signifying increased momentum and interest in the DEP platform."

Antibody-drug conjugates (ADCs) have become an increasingly valuable class of therapeutic agents in oncology and hematology. The design of ADCs incorporates the specific cell targeting property of antibodies with the cell killing properties of chemically conjugated drugs, to provide a targeted therapeutic with minimal off target toxicities.

Starpharma’s DEP ADCs have the potential to overcome the limitation of relatively low drug loading that is a feature of first-generation ADCs. The DEP technology allows precise attachment of drug loaded dendrimer(s) to targeting molecules with a high load of covalently link drug (4, 8,16, 32 drug molecules per dendrimer) providing a selective, homogeneous ADC with a significantly higher drug-antibody ratio (DAR) as compared to currently available ADCs.

Starpharma has previously demonstrated the advantages of DEP in ADCs in multiple preclinical studies, including for DEP HER-2 ADC, which showed significant tumour regression and 100% survival, outperforming Herceptin & Kadcyla in a human ovarian cancer model. DEP ADCs are the subject of both internal and partnered DEP programs.

Starpharma has multiple DEP partnerships with leading, international companies, including AstraZeneca, MSD, and Chase Sun, and the company’s DEP technology has already yielded four clinical-stage oncology products.