On March 30, 2023 RedHill Biopharma Ltd. (NASDAQ: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that it has entered into a definitive agreement for the purchase and sale of 1,500,000 of the Company’s American Depositary Shares ("ADSs") (or ADS equivalents), each ADS representing four hundred (400) ordinary shares, series A warrants to purchase up to an aggregate of 1,500,000 ADSs and series B warrants to purchase up to an aggregate of 1,500,000 ADSs at a purchase price of $4.00 per ADS (or ADS equivalent) and associated warrants, in a registered direct offering (Press release, RedHill Biopharma, MAR 30, 2023, View Source [SID1234629630]). The series A warrants have an exercise price of $4.75 per ADS, are exercisable immediately and have a term of five years following issuance, and the series B warrants have an exercise price of $4.00 per ADS, are exercisable immediately and have a term of nine months following issuance. The closing of the offering is expected to occur on or about April 3, 2023, subject to the satisfaction of customary closing conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds to the Company from this offering are expected to be $6 million, before deducting the placement agent’s fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from this offering for general working capital, acquisitions, research and development, and general corporate purposes.

The securities described above are being offered by the Company pursuant to a "shelf" registration statement on Form F-3 (File No 333-258259) previously filed with the Securities and Exchange Commission (the "SEC") on July 29, 2021, and declared effective by the SEC on August 9, 2021. The offering of the securities is made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the securities being offered will be filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 865-5711 or e-mail at [email protected].

The Company also has agreed that certain existing warrants to purchase up to an aggregate of 330,106 ADSs at an exercise price of $59.20 per share and a termination date of November 11, 2027 will be amended, effective upon the closing of the offering, so that the amended warrants will have a reduced exercise price of $4.75 per share and a termination date of five years following the closing of the offering.

On March 30, 2023 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR) , a late-stage biopharmaceutical company developing and commercializing first-in-class critical care products, reported that Maxim Group LLC will serve as financial advisor to its wholly-owned subsidiary, Citius Acquisition Corp. Inc., in connection with the intended formation of a separate publicly-traded entity to commercialize and grow Citius’ oncology asset, I/ONTAK (Press release, Citius Pharmaceuticals, MAR 30, 2023, View Source [SID1234629629]). The U.S. Food and Drug Administration (FDA) is currently reviewing a biologics license application (BLA) for I/ONTAK and has set a targeted decision date (PDUFA) of July 28, 2023.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Citius is committed to maximizing the value of I/ONTAK and advancing our pipeline. Maxim Group has a strong track record of executing strategic and financial transactions in the life science sector, and we look forward to working closely with them to optimize the structure and timing of contemplated I/ONTAK transactions," stated Leonard Mazur, Chairman and CEO of Citius.

Any transactions would be subject to the satisfaction of customary conditions, including final approval from the Citius Board of Directors, regulatory approvals, and SEC filings. Upon closing of the transactions, Citius would continue to trade on the Nasdaq exchange under its current ticker CTXR.

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction. There can be no assurance regarding the ultimate timing of proposed transactions or that the transactions will be completed at all.

On March 30, 2023 Everest Medicines (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on developing, manufacturing and commercializing transformative pharmaceutical products and vaccines, reported its financial results for the full year ended December 31, 2022, along with a corporate update (Press release, Everest Medicines, MAR 30, 2023, View Source [SID1234629628]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Despite a challenging external capital environment in 2022, we made solid advancements in our key therapeutic areas toward becoming a fully integrated biopharmaceutical company," said Rogers Yongqing Luo, CEO of Everest Medicines. "We received NDA approval for Xerava in China this month and successfully filed for New Drug Application for Nefecon in mainland China with Breakthrough Therapy Designation and Priority Review status, while also receiving fast-track review designations in other Asian territories for Nefecon. We reported positive topline results from multiple clinical studies and achieved the first pre-clinical proof-of-concept milestone from our self-discovery programs. Moreover, our state-of-the-art mRNA vaccine manufacturing facility began production and successfully completed trial runs. The company’s loss in 2022 was reduced by RMB 760 million compared with the previous year. We head into 2023 with a strong balance sheet of US$432 million, along with a clear new strategy for the future."

"2023 is set to be an exciting year for Everest, as the commercialization of our first product will propel the Company from a clinical-stage biotech to a commercial-stage biopharmaceutical company. We will establish a highly efficient commercial team to bring important novel treatments such as Xerava and Nefecon to Chinese patients as soon as possible. We also strive to make significant progress in clinical and regulatory development, internal R&D and business development across our key therapeutic areas of renal diseases and infectious diseases, as well as to our mRNA platform. We anticipate at least three more drug candidates to receive NDA approval in China over the next two years, which will bring very promising commercial prospects," said Luo.

Recent Product Highlights and Anticipated Milestones

INFECTIOUS DISEASE PORTFOLIO

Xerava (Eravacycline), is a novel, fully synthetic fluorocycline intravenous antibiotic for the treatment of infections caused by susceptible gram-positive, gram-negative and anaerobic pathogens including those multidrug resistant ("MDR") isolates.

2022:

⎯ In August, the Company announced that the Taiwan Food and Drug Administration had accepted its submission of an NDA for Xerava (eravacycline) for the treatment of complicated intra-abdominal infections (cIAI). In addition, the Company entered into an exclusive partnership agreement with TTY for the commercialization of Xerava in Taiwan.

⎯ In October, the Company announced that the Department of Health of the Hong Kong Special Administrative Region, China, approved an NDA for Xerava for the treatment of cIAI in adult patients in Hong Kong.

2023:

⎯ In March, the Company announced that NMPA of China approved its NDA for Xerava for the treatment of cIAI in adult patients.

⎯ We expect NDA approval of eravacycline for the treatment of cIAI in Taiwan region in 2023.

Taniborbactam, is a beta-lactamase inhibitor ("BLI") that, in combination with cefepime, may offer a potential treatment option for patients with serious bacterial infections caused by difficult-to-treat resistant gram-negative bacteria, most notably carbapenem- resistant Enterobacterales ("CRE") and carbapenem-resistant Pseudomonas aeruginosa ("CRPA"), particularly for those resistance caused by metallo beta-Lactamases.

– In March 2022, our licensing partner, Venatorx Pharmaceuticals ("Venatorx"), reported positive results from its pivotal phase 3 study, CERTAIN-1 (Cefepime Rescue with taniborbactam in cUTI), evaluating cefepime-taniborbactam, an investigational new drug, versus meropenem as a potential treatment for hospitalized adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis.

– We expect to file NDA for taniborbactam for the treatment of cUTI in China in 2023.

EVER206 (also known as SPR206) is a potentially best-in-class, novel polymyxin derivative designed to reduce toxicity, especially nephrotoxicity, compared to the levels observed clinically with polymyxin B and colistin.

⎯ In January 2023, the Company announced topline results from a China phase 1 study on healthy subjects demonstrating that EVER206 is well-tolerated with no evidence of acute kidney injury and no new safety signals on healthy subjects with dose ranges applied in the study. The pharmacokinetics of healthy subjects in China were comparable to the results of the overseas phase I study (SPR206-101) and the safety profile was also similar to the results from the overseas Phase I trial, supporting Everest’s plans to initiate next-phase clinical development in China soon.

⎯ We expect to initiate the phase 3 trial of EVER206 in 2023.

RENAL PORTFOLIO

Nefecon, our anchor drug candidate in the renal therapeutic area, is a novel oral formulation of budesonide in development for the treatment of primary IgAN.

2022:
⎯ In April, the Company announced the findings of reduction in proteinuria and stabilization of estimated glomerular filtration rate ("eGFR") in a Chinese subpopulation after nine months of treatment with Nefecon are in line with topline results from Part A of the pivotal global phase 3 clinical trial NefIgArd, which were reported in November 2020 by Calliditas.

⎯ In July, our partner Calliditas was granted conditional marketing authorization for Kinpeygo (brand name of Nefecon in Europe) by the European Commission for the treatment of primary IgAN in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/gram.

⎯ In November, the Company received an acceptance from the China NMPA for its NDA of Nefecon for the treatment of primary IgAN in adults at risk of rapid disease progression.

⎯ In November, the Company announced the Taiwan Food and Drug Administration granted Accelerated Approval Designation to Nefecon and the MFDS in South Korea granted Orphan Drug Designation to Nefecon.

2023:
⎯ In Jan., CDE of the China NMPA granted Priority Review for the NDA of Nefecon.

⎯ In February, South Korea’s MFDS granted Global Innovative product on Fast Track ("GIFT") designation to Nefecon for the treatment of primary IgAN. Nefecon is the second product and the first non-oncology product included in MFDS’s GIFT program. Inclusion of the GIFT program is expected to accelerate regulatory review time by 25% and allow for rolling review.

⎯ In March, our partner Calliditas reported positive topline results from Phase 3 NefIgArd Trial evaluating Nefecon in IgAN. The trial met its primary endpoint with Nefecon demonstrating a highly statistically significant benefit over placebo (p value <0.0001) in eGFR over the two-year period of 9-months of treatment with Nefecon or placebo and 15-months of follow-up off drug.

⎯ We expect to receive NDA approval for Nefecon for the treatment of primary IgAN in mainland China and Singapore in 2023.

⎯ We expect to file NDA of Nefecon for the treatment of IgAN in South Korea, Hong Kong and Taiwan region in 2023.

EVER001 is the next-generation covalent reversible Bruton’s tyrosine kinase (BTK) inhibitor in development globally for the treatment of renal diseases.

⎯ In September 2022, the Company announced that the CDE has approved the IND application for a phase 1b study of EVER001, in development for the treatment of glomerular diseases.

mRNA PLATFORM

PTX-COVID19-B, a potentially best-in-class lipid nanoparticle-formulated mRNA COVID-19 vaccine with strong immunogenicity and benign tolerability profiles.

⎯ In October 2022, our partner Providence reported positive topline data from a phase 2 study evaluating the safety, tolerability and immunogenicity of its mRNA COVID-19 vaccine candidate, PTX-COVID19-B. PTX- COVID19-B demonstrated non-inferiority compared to Comirnaty, Pfizer’s and BioNTech’s U.S. Food and Drug Administration ("FDA") – approved mRNA vaccine, with respect to the geometric mean titer ratio of neutralizing antibodies observed two weeks after the second of two intramuscular injections. Additionally, PTX-COVID19-B was generally well-tolerated, with a safety and tolerability profile similar to Comirnaty. This phase 2 study provides important clinical validation of our mRNA technology platform.

EVER-COVID19-M1, is an Omicron-targeting bivalent COVID-19 booster vaccine candidate.

⎯ The Company is working on an Omicron-containing bivalent booster candidate — EVER-COVID19-M1, and initiated rolling submission of IND applications for phase 1 and 2 study which may enable potential emergency use authorization application.

mRNA rabies vaccine

⎯ In December 2022, the Company announced it had achieved the pre-clinical proof-of-concept milestones for the mRNA rabies vaccine program. The rabies program is the first non-COVID 19 vaccine developed with our clinically- validated mRNA platform, highlighting the in-house discovery capabilities of the Company.

OTHER CLINICAL-STAGE ASSETS

⎯ In May 2022, our licensing partner Pfizer Inc. presented detailed results from two pivotal studies that make up the ELEVATE UC phase 3 registrational program evaluating etrasimod, a once-daily, oral, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately-to-severely active ulcerative colitis ("UC"). Both Phase 3, multi-center, randomized, placebo-controlled trials achieved all primary and key secondary endpoints, with etrasimod demonstrating a safety profile consistent with previous studies.

⎯ In December 2022, our licensing partner Pfizer received acceptance from the U.S. FDA for the review of an NDA for etrasimod for individuals living with moderately-to-severely active UC. The FDA’s decision is expected in the second half of 2023. This anticipated U.S. FDA approval will be the first approval of etrasimod globally. In addition, the European Medicines Agency accepted the Marketing Authorization Application for etrasimod in the same patient population, with the decision anticipated in the first half of 2024.

⎯ We are conducting a phase 3 study in Asia for etrasimod for the treatment of moderate-severe UC, which is expected to complete enrollment in 2023.

Business Development Updates

⎯ In March 2022, the Company entered into a license agreement with Calliditas to develop and commercialize Nefecon for the treatment of primary IgAN in South Korea, expanding its license in addition to rights held in Greater China and Singapore.

⎯ In August 2022, the Company announced that it entered into an agreement with Immunomedics, Inc. ("Immunomedics"), a wholly-owned subsidiary of Gilead, whereby Immunomedics will obtain exclusive rights to develop and commercialize Trodelvy (sacituzumab govitecan) in Greater China, South Korea, Singapore, Indonesia, Philippines, Vietnam, Thailand, Malaysia and Mongolia (the "Agreement"). Under the terms of the Agreement, the Company will receive up to US$455 million in total considerations with US$280 million in upfront payments payable subject to, among other things, certain regulatory approvals and up to US$175 million in potential future milestone payments. In addition, the Company will be released from payment obligations for up to US$710 million in remaining milestone payments.

Drug Discovery

Our discovery team is focused on precision disease-modifying mechanisms in key pathogenic pathways in kidney diseases and promising mRNA vaccines such as prophylactic vaccines for infectious disease and therapeutic cancer vaccines against solid tumors. Our mRNA rabies vaccine program achieved pre-clinical proof-of-concept in December 2022 as the first of several non-COVID-19 mRNA vaccine/therapeutics candidates that have demonstrated our discovery capabilities.

Manufacturing facility

The company’s state-of-the-art mRNA manufacturing facility in Jiashan, Zhejiang Province initiated operation and successfully carried out trial production runs in December 2022. The first phase of the project, covering an area of 58,000 square meters, has a set of advanced production facilities built to meet global and China GMP standards, and designed with an annual production capacity of 700 million doses of mRNA vaccines.

Commercialization

The regulatory approval of Xerava in Singapore was the first product approval wholly applied by and granted to Everest, and Xerava is our first marketed product. As the company transforms to a fully-integrated biopharma, we are building out a highly efficient and industry-leading commercial team, focusing on the therapeutic areas of internal medicines and infectious diseases. We expect to commercially launch Xerava in mainland China in Q3 2023 and the commercial team will be further expanded when approaching the expected approval of Nefecon in mainland China. In addition, under the supporting policies of the Boao Lecheng International Medical Tourism Pilot Zone, our commercial team is working on an early access program of Nefecon to bring benefits to patients sooner.

Financial Highlights

IFRS Numbers:

Total assets of RMB 6.61 billion and net assets of RMB 5.65 billion for the year ended December 31, 2022.
Revenue increased by RMB12.7 million to RMB12.8 million for the year ended 31 December 2022, from RMB54,000 for the year ended 31 December 2021, primarily due to the sales of eravacyline and Trodelvy in Singapore.
Research and development (the "R&D") expenses increased by RMB196.3 million to RMB809.7 million for the year ended 31 December 2022, from RMB613.4 million for the year ended 31 December 2021, primarily due to i) additional clinical trials for our drug candidates; (ii) expansion of internal discovery team to build up in-house R&D capabilities; (iii) increased technical transfer related costs for our drug candidates. R&D expenses related to Trodelvy after August 1, 2022 would be reimbursed by Gilead.
General and administrative expenses increased by RMB33.8 million to RMB276.5 million for the year ended 31 December 2022, from RMB242.7 million for the year ended 31 December 2021, primarily due to increased professional service expenses.
Distribution and selling expenses increased by RMB128.5 million to RMB326.7 million for the year ended 31 December 2022, from RMB198.2 million for the year ended 31 December 2021, primarily due to increased employee benefit expenses and launch and pre-launch activities carried out for commercialization. Distribution and selling expenses related to Trodelvy after August 1, 2022 would be reimbursed by Gilead.
Net loss for the year ended 31 December 2022 was RMB247.3 million, compared with RMB1,008.7 million for the year ended 31 December 2021, primarily due to the other gain of RMB1,322.3 million from Trodelvy transaction.
Cash and cash equivalents and bank deposits amounted to RMB1,651.4 million as of 31 December 2022. Pro forma for the Trodelvy Agreement upfront considerations we received in early 2023, our Cash and cash equivalents and bank deposits amounted to USD432 million.
Non-IFRS Measure:

Adjusted loss for the year[1] was RMB17.4 million for the year ended 31 December 2022, representing a decrease of RMB759.9 million from RMB777.3 million for the year ended 31 December 2021, primarily due to other gain of RMB1,322.3 million from Trodelvy transaction.

On March 30, 2023 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported financial results for the fourth quarter and full year ended December 31, 2022. MTEM also announced a strategic reprioritization and corresponding reduction in workforce, in order to focus on its core clinical development programs and extend its financial runway (Press release, Molecular Templates, MAR 30, 2023, View Source [SID1234629626]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Strategic Reprioritization and Cost-Saving Measures

On March 29, 2023, the Board of Directors of MTEM approved a strategic reprioritization and corresponding reduction in workforce, designed to focus on the clinical development programs for MT-6402 (PD-L1), MT-8421 (CTLA-4), and MT-0169 (CD38), and preclinical activities related to MTEM’s collaboration with Bristol Myers Squibb. This restructuring will reduce MTEM’s workforce by approximately 50%, result in the cessation of the MT-5111 (HER2) clinical development program, and focus the majority of MTEM’s preclinical efforts around activities related to the Bristol Myers Squibb collaboration.

Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated: "These cost-savings measures are a difficult, but necessary, step for MTEM to take in order to continue pursuing the development of these promising programs. We thank all our employees who have worked so hard to bring these programs this far, and we will continue this important work with our refocused strategy and available resources." Dr. Poma added, "We have now seen evidence of monotherapy clinical activity with MT-6402 through two separate mechanisms of action unique to immuno-oncology: the alteration of tumor immunophenotype and the dismantling of the tumor microenvironment (‘TME’). We recently announced the FDA’s acceptance of our Investigational New Drug Application (‘IND’) for MT-8421, a new approach to CTLA-4 that we believe can potently deplete Tregs in the TME without driving immune-related adverse events (‘irAEs’). We look forward to providing further updates on our MT-6402, MT-8421 and MT-0169 programs throughout 2023."

Company Highlights

MTEM expects to provide periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2023.
Clinical data for each program has demonstrated novel mechanisms of action, unique pharmacodynamic ("PD") effects, and single agent activity in heavily relapsed / refractory patients across immuno-oncology, hematologic, and solid tumor indications.
Dose escalation continues for MT-6402. MTEM observed dose-dependent PD effects not seen with PD-(L)1 antibodies and consistent with T-cell activation and TME dismantling. Maximal MDSC depletion was observed at 63 mcg/kg, the highest dose cleared to date. PD effects were seen across patients, irrespective of HLA genotype or level of tumor or immune cell PD-L1 staining.
Seven patients were evaluable for radiographic assessment at the end of cycle 2 in the 63 mcg/kg cohort for MT-6402. One patient with nasopharynx squamous cell carcinoma in this cohort had a PR (RECIST) with a 63% reduction in the index lesion after cycle 2 which was maintained and confirmed at the end of cycle 4 (66% reduction). The patient remains on study.
One patient in cohort 1 (16 mcg/kg) for MT-6402 with non-small cell lung cancer ("NSCLC") demonstrated resolution of three osseous lesions and a reduction in uptake in the remaining lesion. This patient remained on treatment for approximately 8 months.
An IND for MT-8421 was accepted on March 8, 2023, with the first-in-human phase I study anticipated by mid-year 2023. MT-8421 targets CTLA-4-expressing Tregs in the TME for elimination without affecting Tregs in the periphery.
Dose escalation continues for MT-0169. MT-0169 completed the 5 mcg/kg dose escalation cohort (N=4) and the 10 mcg/kg dose escalation cohort (N=3) without any cardiac AEs or dose-limiting toxicities ("DLTs") and is enrolling at 15 mcg/kg. A Very Good Partial Response ("VGPR") was seen in a patient with extramedullary IgA myeloma treated at 5 mcg/kg which improved to a stringent Complete Response at cycle 8. The patient remains on study.
Of the over 100 patients treated across MTEM’s three clinical programs utilizing our de-immunized scaffold to date, there have been no instances of capillary leak syndrome or other manifestations of innate immunity observed.
Nearly all toxicities seen to date appear to be target-mediated with no non-specific scaffold effects noted, apart from occasional episodes of an infusion related reaction. No instances of off-target hematologic toxicity, interstitial lung disease, hepatic toxicity, or ocular toxicity common with antibody-drug conjugates have been observed.
The ETB platform continues to demonstrate clinical validation in terms of both safety and efficacy.
MT-6402 (PD-L1-targeting ETB with Antigen Seeding Technology)

MT-6402 was designed to activate T-cells through direct cell-kill of immunosuppressive PD-L1+ immune cells.
In addition, MT-6402 can deliver and induce the presentation of an MHC class I CMV antigen on tumor cells (antigen seeding mechanism of action) for pre-existing CD8 T-cell recognition and destruction in HLA-A*02/CMV+ patients with high PD-L1 expression on their tumors.
MT-6402 continues to demonstrate PD effects and monotherapy activity in heavily pre-treated checkpoint therapy experienced patients.
Dose escalation continues in the MT-6402 phase I study in relapsed/refractory solid tumor patients with PD-L1-expressing tumors and/or PD-L1 expressing immune cells in the TME.

Highlights from the on-going Phase I study include:

MTEM continues to observe PD effects not seen with PD-(L)1 antibodies and consistent with T-cell activation and TME dismantling. Maximal MDSC depletion was observed at 63 mcg/kg, the highest dose cleared to date. PD effects were seen across patients, irrespective of HLA genotype or level of tumor or immune cell PD-L1 staining.
Seven patients were evaluable for radiographic assessment at the end of cycle 2 in the 63 mcg/kg cohort. One patient in this cohort had a PR (RECIST) with a 63% reduction in the index lesion after cycle 2 which was maintained and confirmed at the end of cycle 4. This is a patient with metastatic squamous cell nasopharynx carcinoma ("NPC") with disease progression after radiation therapy, chemotherapy, and pembrolizumab who had 2% PD-L1 expression and is not HLA-A*02, suggesting that the response is due to T-cell activation through the clearance of PD-L1+ immune cells, a novel mechanism in immuno-oncology. The patient showed a >250% increase in their CD8/CD4 T-cell ratio. The patient remains on study in the fifth month of therapy.
One patient in cohort 1 (16 mcg/kg) with NSCLC demonstrated resolution of three osseous lesions and a reduction in uptake in the remaining lesion. This patient also experienced grade 2 cytokine release syndrome consistent with T-cell activation and was dose reduced to 8 mcg/kg. This patient is the only patient treated thus far with high tumor PD-L1 expression who is also HLA-A*02/ CMV+ and hence appropriate for the antigen seeding mechanism of action. Antigen seeding and the alteration of tumor immunophenotype is a novel mechanism in immuno-oncology unique to the ETB scaffold.
Treatment-related AEs including immune-related AEs have been largely restricted to grade 1-2. The 63 mcg/kg dose was well-tolerated and dose escalation continues at 83 mcg/kg.
Two Phase I dose expansion cohorts are planned for 2023 including for patients with high PD-L1 tumor expression and for patients with low PD-L1 tumor expression.
MT-8421 (CTLA-4 ETB)

MT-8421 was designed to target CTLA-4 in a wholly distinct manner from the current monoclonal antibody approaches. MT-8421 was designed to eliminate CTLA-4-expressing Tregs in the TME through a direct cell-kill mechanism independent of the effector cell presence that antibodies rely upon.
MT-8421 was also designed to avoid CTLA-4 blockade in the periphery, the major mechanism of antibody-mediated autoimmune toxicity.
MTEM has received clearance by the United States Food and Drug Administration ("FDA") following review of its IND to proceed for clinical testing of its novel MT-8421 ETB program targeting CTLA-4 in patients with relapsed/refractory solid tumors previously exposed to checkpoint inhibitors.
MTEM expects to initiate a first-in-human Phase I study with MT-8421 by mid-year 2023.
MT-0169 (CD38 ETB)

MT-0169 was designed to destroy CD38+ tumor cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and immunogenic cell death). Highlights from the on-going Phase I include:
The 5 mcg/kg cohort completed recruitment (N=4) and analysis with no related AEs higher than grade 1 and no cardiac AEs.
A VGPR was seen in a patient with extramedullary IgA myeloma treated at 5 mcg/kg. The patient had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative, and significant improvement of hemoglobin to normal values without transfusion. The patient’s disease was quad-agent refractory including CD38-targeting, proteosome inhibitor, IMiD, and a BCMA bispecific antibody. The patient’s response improved to a stringent Complete Response and they remain on study.
Dose escalation completed with three patients enrolled at 10 mcg/kg and no related AE’s higher than grade 2.
Dose escalation is now proceeding at 15 mcg/kg.
Key Milestones for 2023

Accelerating enrollment across all clinical programs with advancement into later stage trials expected in 2023
Initiation of first-in-human Phase I study for MT-8421
Advancement of Bristol Myers Squibb research collaboration across multiple targets
Conferences

MTEM participated in the Breast and Lung Cancer Panel at TD Cowen 43rd Annual Health Care Conference, which took place in Boston, Tuesday, March 7, 2023, 10:30am – 11:30am ET. The webcast can be accessed here and in the "News and Media" section of the corporate website.
MTEM presented a fireside chat at the virtual Oppenheimer 33rd Annual Healthcare Conference, which took place Wednesday, March 15, 2023, 12:40am ET. The webcast can be accessed here and in the "News and Media" section of the corporate website.
MTEM will present an abstract, "Engineered Toxin Bodies (ETBs): Clinical stage immunotoxins with a safer and differentiated profile", Monday, April 17, 2023, 1:30pm – 5pm ET (Section 13, Poster Board No 29, No. 2661), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting taking place at the Orange County Convention Center in Orlando, FL from April 14 – 19, 2023.
Financial Results

The net loss attributable to common shareholders for the fourth quarter of 2022 was $22.0 million, or $0.39 per basic and diluted share. This compares with a net loss attributable to common shareholders of $10.2 million, or $0.18 per basic and diluted share, for the same period in 2021.

Revenues for the fourth quarter of 2022 were $2.6 million, compared to $18.0 million for the same period in 2021. Revenues for the fourth quarter of 2022 were comprised of revenues from collaborative research and development agreements with Bristol Myers Squibb.

Total research and development expenses for the fourth quarter of 2022 were $17.6 million, compared with $19.3 million for the same period in 2021. Total general and administrative expenses for the fourth quarter of 2022 were $6.1 million, compared with $7.9 million for the same period in 2021.

As of December 31, 2022, MTEM’s cash and investments totaled $61.0 million, including borrowings of $35.0 million under its K2 Loan and Security Agreement whose scheduled maturity date for repayment is June 1, 2024, subject to continued compliance with the financial covenant and solvency requirements therein. MTEM is currently in compliance with such covenant and requirements, and expects to continue to be in compliance into the fourth quarter of 2023. Any default of the financial covenant or solvency requirements would potentially trigger accelerated repayment. Subject to MTEM’s continued compliance with the K2 Loan and Security Agreement, MTEM anticipates a cash runway into the second quarter of 2024.

On March 30, 2023 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported its financial results for the full year 2022, its recent business highlights, and a preview of select anticipated milestones (Press release, Surgimab, MAR 30, 2023, View Source [SID1234629625]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2022, we achieved significant milestones in both our internal pipeline and strategic collaborations, while strengthening our management team with the appointment of Anne Borgman, M.D., as Chief Medical Officer," said Bill Newell, Sutro’s Chief Executive Officer. "We are delighted with the recent data updates for our lead candidate, luvelta, in advanced ovarian cancer and rare pediatric AML, and are excited to progress it into a planned registration-directed study in ovarian cancer in the second quarter of this year. As we look to the future, we remain confident in our ability to drive value and deliver on our mission to develop next-generation therapies that have the potential to transform the lives of cancer patients."

Recent Business Highlights and Select Anticipated Milestones

STRO-002, International Nonproprietary Name, "luveltamab tazevibulin" or abbreviated as "luvelta", FolRα-Targeting ADC: Luvelta is being studied in the clinic, in the U.S. and Europe, for patients with ovarian and endometrial cancers.

Sutro plans to initiate REFRaME, a Phase 2/3 registration-directed study for patients with platinum-resistant ovarian cancer, in the second quarter of 2023, as discussed with the U.S. Food and Drug Administration (FDA). Once results are collected on approximately 110 patients in the selected dose of the luvelta arm, Sutro plans to apply for accelerated approval based on overall response rate (ORR) as the primary endpoint. At the end of the trial, full approval can be sought based on progression free survival (PFS) as the primary endpoint, comparing the luvelta arm and the standard of care arm.
In January 2023, the company announced results from the luvelta Phase 1 dose-expansion study demonstrating that FolRα-selected patients–-defined as patients with TPS >25%–-experienced meaningful clinical benefit, with 43.8% ORR, median duration of response (DOR) of 5.4 months, and median PFS of 6.6 months for those receiving the higher starting dose of 5.2 mg/kg. The safety profile is generally consistent with prior data; asymptomatic neutropenia was the primary adverse event and no new safety signals were observed. Interim data from an exploratory cohort, with 5.2 mg/kg doses of luvelta together with prophylactic pegfilgrastim, appear to demonstrate reduced dose delays and lower incidences of Grade 3+ neutropenia.
Patients with CBFA2T3::GLIS2 (CBF/GLIS) AML, a highly refractory and uniformly fatal subtype of acute megakaryoblastic leukemia found exclusively in infants and young children, were treated with luvelta under compassionate use. During the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2022), an oral presentation was given by the investigator who aggregated the experiences of patients who were treated.
Additional ongoing clinical studies for luvelta include a combination study with bevacizumab for patients with advanced ovarian cancer and a dose-expansion study for patients with endometrial cancer. Translational work is ongoing to support an Investigational New Drug (IND) for the initiation of a non-small cell lung cancer (NSCLC) study, for which submission is planned in 2023.
STRO-001, CD74-Targeting ADC: The Phase 1 study for patients with B-cell malignancies has been completed in the global sites ex-Greater China and clinical studies in Greater China have been initiated.

Sutro has completed the Phase 1 dose-escalation study in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM), after reaching a maximum tolerated dose (MTD). Sutro plans to leverage the clinical data produced by its partner BioNova Pharma (BioNova) in Greater China to make decisions regarding further clinical development, based on a prioritization assessment.
BioNova is advancing clinical development of BN301 (STRO-001) for patients with hematological malignancies in Greater China. In February 2023, BioNova announced that the first patient had been dosed in the Phase 1 clinical study of BN301 (STRO-001) for the treatment of advanced B-cell Non-Hodgkin’s Lymphoma (NHL).
Additional Pipeline Programs: A Sutro Research Forum, held in 2022, highlighted STRO-003 and Sutro’s emerging research portfolio.

STRO-003 is an advanced ADC that has been designed to target ROR1, takes advantage of innovative linker-warhead technology and features eight precisely placed β-Glucuronidase-cleavable linkers attached to next-generation exatecan warheads, known for their ability to inhibit topoisomerase-1 (TOPO-1) and cause DNA disruption.
STRO-003 has demonstrated in NSCLC and breast cancer patient-derived xenograft models strong cell-killing activity in low and heterogeneous expressing tumors. STRO-003 has exhibited promising tolerability in preclinical studies involving rodents and non-human primates, potentially reducing lung toxicity, a concern that is commonly associated with TOPO-1 class payload ADCs. Preparations are underway for IND enabling studies for STRO-003, which we expect will be completed in the first quarter of 2024.
Sutro provided details on its product and process design, which enables its emerging portfolio including novel therapeutic modalities—for example, a single antibody which can be conjugated site-specifically to deliver two different payloads with synergistic mechanisms.
Collaboration Updates: Sutro continues to seek to maximize the value of its proprietary cell-free platform by working with partners on programs in multiple disease spaces and geographies and has generated from collaborators an aggregate of approximately $621 million in payments through December 31, 2022, including equity investments.

In December 2022, Sutro and Vaxcyte expanded upon a nearly decade-long relationship through a new agreement, under which Vaxcyte acquired an option to access expanded rights to develop and manufacture cell-free extract, among other rights, and includes a $22.5 million upfront payment and, upon exercise of the option, up to an additional $135 million in option exercise and contingent payments. In October 2022, Vaxcyte reported positive topline data from the Phase 1/2 proof-of-concept study of its 24-valent pneumococcal conjugate vaccine candidate (VAX-24) under investigation for the prevention of invasive pneumococcal disease in adults aged 18-64. Under an existing license agreement with Vaxcyte, Sutro is eligible to receive four percent (4%) royalties on worldwide net sales of any licensed vaccine candidates for human health use, including VAX-24.
Sutro’s collaboration with Astellas on the discovery of immunostimulatory antibody-drug conjugates (iADCs) for three targets is ongoing, for which Sutro receives financial support for its research efforts, potential milestone payments and royalties, and has an option to co-develop and co-commercialize product candidates in the U.S.
Sutro is manufacturing initial drug supply for the clinical development of Merck’s MK-1484, currently in a Phase 1; and clinical trial materials for Bristol Myers Squibb’s (BMS) CC-99712, a BCMA-targeting ADC for treatment of multiple myeloma, currently in Phase 1.
Sutro is providing clinical drug supply to BioNova for clinical studies for BN301 (STRO-001) in Greater China. Sutro is currently supporting Tasly Biopharmaceuticals (Tasly) for initiation of clinical development activities and an IND filing in Greater China for STRO-002 and will provide initial clinical drug supply.
Corporate Updates: Sutro strengthened and continues to build a world-class leadership team through the appointment of a new Chief Medical Officer and internal promotions.

Anne Borgman, M.D., joined Sutro as Chief Medical Officer in February 2023 overseeing the Clinical Development & Regulatory teams, with focus on the development of luvelta and clinical strategy for Sutro’s proprietary pipeline, in addition to being a member of Sutro’s Senior Management Team.
Sutro bolstered the Senior Management Team with the promotion of Brunilda Shtylla to Chief Business Officer, who leads Business Development. Devendra Luhar was promoted to SVP, Manufacturing & San Carlos Facility, and Carlos Lugo Ponce was promoted to SVP, Quality Control & Quality Assurance.
Full Year 2022 Financial Highlights

Cash, Cash Equivalents and Marketable Securities
As of December 31, 2022, Sutro had cash, cash equivalents and marketable securities of $302.3 million, as compared to $287.3 million as of September 30, 2022, and approximately 0.7 million shares of Vaxcyte common stock with a fair value of $32.0 million, which together provide a projected cash runway into the second half of 2024, based on current business plans and assumptions.

Unrealized Gain from Increase in Value of Vaxcyte Common Stock
The non-operating, unrealized gain of $12.1 million for the year 2022 was due to the increase since December 31, 2021 in the estimated fair value of Sutro’s holdings of Vaxcyte common stock. Vaxcyte common stock held by Sutro will be remeasured at fair value based on the closing price of Vaxcyte’s common stock on the last trading day of each reporting period, with any non-operating, unrealized gains and losses recorded in Sutro’s statements of operations. Sutro sold approximately 1.1 million shares of Vaxcyte common stock during 2022.

Revenue
Revenue was $67.8 million for the year ended December 31, 2022, as compared to $61.9 million for the same period in 2021, with the 2022 amount related principally to recognition of the upfront payment from Tasly, the milestone payment from Merck, and the Astellas, BMS, and EMD Serono collaborations and BioNova agreement. Future collaboration and license revenue under existing agreements and from any additional collaboration and license partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones, and other agreement payments.

Operating Expenses
Total operating expenses for the year ended December 31, 2022 were $196.7 million, as compared to $160.4 million for the same period in 2021. The year 2022 includes non-cash expenses for stock-based compensation of $26.3 million and depreciation and amortization of $5.7 million, as compared to $23.2 million and $4.8 million, respectively, in the comparable 2021 period. Total operating expenses for the year ended December 31, 2022 were comprised of research and development expenses of $137.2 million and general and administrative expenses of $59.5 million, which are expected to increase in 2023 as Sutro’s internal product candidates advance in clinical development and additional general and administrative expenses are incurred as a public company.