On November 10, 2022 Vaccitech plc (NASDAQ: VACC) reported its financial results for the third quarter ended September 30, 2022 and provided an overview of the Company’s recent corporate developments (Press release, Vaccitech, NOV 10, 2022, View Source [SID1234623731]). Vaccitech is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, autoimmunity, and cancer.

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"This has been a very exciting quarter at Vaccitech. During the past three months we have made significant progress on our clinical programs, strengthened our balance sheet and leadership team, and continued to actively engage with investors," remarked Bill Enright, CEO of Vaccitech. "We dosed the first patient in our Phase 2b clinical trial of VTP-300 in HBV and reported the findings of our Phase 1b/2a study of VTP-300 at the American Association for the Study of Liver Disease (AASLD) Liver meeting. In addition, we published a paper in Cell showing the activation of two key pathways with intravenous (IV) vaccination of a SNAPvax construct, which led to improved T cell mediated tumor killing in a pre-clinical model. We were also very pleased to announce the promotion of Gemma Brown to the role of CFO. I would also like to note that that this quarter’s royalty and milestone payments from the sales of Vaxzervria, AstraZeneca’s COVID-19 vaccine, have assisted in extending our cash runway into the first quarter of 2025. All told, this was a very active quarter for us, and we look forward to continuing our progress and outreach in the coming quarter and year."

"We have made excellent progress in our clinical programs in the past quarter and expect to reach a number of important clinical milestones in 2023," stated Dr. Meg Marshall, Chief Medical Officer of Vaccitech. "We expect to have initiated our Phase 1/2a clinical study in the fourth quarter of 2022 with the first patient first visit (FPFV) for VTP-850, our prostate cancer program, early in the first quarter of 2023, and FPFV for VTP-1100, our HPV-Cancer program, early in the third quarter of next year. FPFV for VTP-1000, our program in Celiac disease, is slated for the fourth quarter of 2023. We also plan to present data from multiple ongoing studies of VTP-300 in HBV next year as well. So, we are looking forward to a 2023 filled with exciting clinical advances."

Third Quarter 2022 Financial Highlights

·Cash position: As of September 30, 2022, cash and cash equivalents were $200.1 million, compared to $214.1 million as of December 31, 2021. The cash burn from operating activities was $43.9 million, being the net of R&D and G&A spend offset by the cash received from revenue recognized in respect of sales of Vaxzevria. $5.2 million of net cash was used in investing activities, which includes the buildout of the state of the art laboratory and Corporate Headquarters in Harwell, United Kingdom, where the Company relocated in the third quarter of 2022.

·Revenues: Revenues comprised primarily of the Company’s share of milestone and royalty payments received by OUI from AstraZeneca related to commercial sales of Vaxzevria. Revenues were $6.2 million in the third quarter of 2022 compared to $17.1 million in the second quarter of 2022, with the reduction attributable to no milestones being achieved in the third quarter of 2022.

General and administrative expenses: General and administrative expenses were a gain of $11.1 million (after including a foreign exchange gain of $18.7 million) in the third quarter of 2022, compared to a gain of $6.4 million (after including a foreign exchange gain of $15.2 million) in the second quarter of 2022. Excluding the foreign exchange gain, G&A expenses were $7.6 million in the third quarter of 2022, which were mainly attributable to personnel expenses of $2.8 million, including the share-based payment charge of $0.6 million, insurance costs of $1.5 million, and legal and professional fees of $2.3 million. Excluding the foreign exchange gain, G&A expenses for the second quarter were $8.8 million and were mainly attributable to personnel expenses of $4.3 million, including the share-based payment charge of $2.1 million, insurance costs of $1.6 million, and legal and professional fees of $1.0 million.

·Net Income: For the third quarter of 2022, the Company generated a net income attributable to its shareholders of $8.2 million, or $0.22 both per fully diluted share and per basic share, compared to a net income attributable to shareholders of $15.7 million, or $0.41 per fully diluted share and $0.42 per basic share, for the second quarter of 2022.

Recent Corporate Developments

Clinical developments:

·On October 31, 2022, we announced the dosing of the first patient in HBV003, a phase 2b clinical trial of VTP-300 to evaluate the optimal timing of low dose nivolumab and impact of additional doses of the MVA boost for a sustained decline in HBsAG.

Pre-clinical developments:

·On October 27, 2022, we announced the publication of research from VTP-1100 in Cell that demonstrates anti-tumor activity achieved with intravenous (IV) vaccination of a SNAPvax construct in an animal model. The study demonstrates that IV administration of SNAPvax primes and expands antigen-specific T cells and reverses suppression in the tumor microenvironment, which promotes T cell infiltration and tumor cell killing. An Investigational New Drug (IND) application submission is expected during the first half of 2023 for HPV related cancer.
·On November 7, 2022 Dr. Young-Suk Lim, Professor of Gastroenterology in the Liver Center at University of Ulsan College of Medicine, presented a poster reporting Phase 1b/2a clinical trial data on VTP-300 at AASLD. The poster presentation showed VTP-300 immunotherapy, as monotherapy and when combined with low dose nivolumab at the boosting time point, was immunogenic and showed a sustained reduction in HBsAg in well-controlled CHB patients, and was administered with no treatment related SAEs and infrequent transient transaminitis. Two of five patients dosed in cohort 3 (ChAdOx1-HBV + MVA-HBV with low dose nivolumab given at the boost) with starting HBsAg levels below 100 achieved non-detectable levels of surface antigen at the data cutoff.

Company Leadership:

·On September 20, 2022, we announced the promotion of Gemma Brown to Chief Financial Officer.

Upcoming Milestones

·In addition to the recent developments detailed above, in the fourth quarter of 2022 the Company expects to

§Open a Phase 1/2 clinical trial of VTP-850 in patients with prostate cancer

·In the first quarter of 2023, the Company

§Intends to conduct an interim efficacy review of HPV001, a Phase 1b/2 clinical trial of VTP-200, a potential treatment for low grade HPV-related cervical lesions
§Expects to have FPFV for VTP-850 in our prostate cancer program
§Intends to move its U.S. team into a new, state of the art facility in Germantown, Maryland

·In 2023, the Company expects to

§Submit IND applications for its two lead SNAPvax candidates, VTP-1000 for the treatment of celiac disease and VTP-1100 for the treatment of HPV-associated cancers
§Have FPFV for VTP-1100 in our HPV cancer program
§Have FPFV for VTP-1000 in our Celiac disease program
§Present data from multiple ongoing clinical studies at AASLD and The European Association for the Study of the Liver (EASL) conferences

·Research and development expenses: Research and development expenses were $9.7 million in the third quarter of 2022 compared to $9.7 million in the second quarter of 2022, showing consistent total spend as we continue to advance our pipeline. The quarter on quarter R&D expense per program is outlined in the following table.

On November 10, 2022 Yumanity Therapeutics, Inc. ("Yumanity" or the "Company") (Nasdaq: YMTX) reported that the registration statement on Form S-4 (the "Registration Statement"), relating to the previously announced asset sale to Janssen Pharmaceutica NV ("Janssen") and merger with Kineta, Inc. ("Kineta"), has been declared effective by the U.S. Securities and Exchange Commission (Press release, Kineta, NOV 10, 2022, View Source;utm_medium=rss&utm_campaign=kineta-announces-effectiveness-of-registration-statement-on-form-s-4-in-connection-with-proposed-reverse-merger-with-yumanity-therapeutics-ymtx [SID1234623730]).

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In June 2022, the Company announced definitive agreements for two strategic transactions. The first definitive agreement is an asset purchase agreement for the sale of Yumanity’s lead clinical-stage product candidate, YTX-7739, as well as Yumanity’s unpartnered discovery-stage neuroscience product candidates and targets to Janssen, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, for $26 million in cash. In connection with the closing of the proposed transaction, Yumanity plans to distribute the remaining available cash proceeds from the sale to Yumanity stockholders via a one-time dividend, net of any amounts retained for outstanding obligations and net cash requirements associated with the proposed merger between Yumanity and Kineta. The amount of such dividend will depend on many factors and will not be determined until closer to the closing date.

Under the second definitive agreement, Kineta will become a wholly-owned subsidiary of Yumanity in an all-stock transaction, resulting in a combined publicly traded company re-named Kineta, Inc., that will focus on developing next-generation immunotherapies that address cancer immune resistance and continue Yumanity’s ongoing research collaboration with Merck & Co. in amyotrophic lateral sclerosis and frontotemporal lobar dementia. Upon completion of the proposed merger, on a pro forma basis and based upon the number of Yumanity shares to be issued in the proposed merger, and after giving effect to a concurrent private investment in public equity ("PIPE") led by Growth & Value Development Inc. for an aggregate purchase price of approximately $30.0 million, current Kineta stockholders are expected to own approximately 68.2% of the combined company, current Yumanity stockholders are expected to own approximately 12.0% of the combined company, and the PIPE investors are expected to own approximately 19.8% of the Yumanity common stock. The actual allocation will be subject to adjustment based on each company’s outstanding equity ownership and Yumanity’s net cash balance at the time of the closing of the proposed merger.

Yumanity will mail the definitive proxy statement/prospectus (the "Proxy Statement") to stockholders of record as of the close of business on November 4, 2022. The Proxy Statement contains a notice and will be accompanied by a voting instruction form or a proxy card relating to the special meeting of Yumanity’s stockholders to approve the asset sale and merger (the "Special Meeting") which will be held in a virtual-only format via live audio webcast at 10:00 a.m. Eastern Time, on December 13, 2022, at www.virtualshareholdermeeting.com/YMTX2022SM, unless postponed or adjourned to a later date.

If the proposals at the Special Meeting are approved, the parties anticipate that the asset sale to Janssen and merger with Kineta will close and the combined company will commence trading on Nasdaq under the new ticker symbol "KA" shortly thereafter, subject to the satisfaction or waiver, as applicable, of all other closing conditions.

Every stockholder’s vote is important, regardless of the number of shares held. Accordingly, Yumanity requests that each stockholder complete, sign, date and return a proxy card (online or by mail) as soon as possible to ensure that the stockholder’s shares will be represented at the Special Meeting. Stockholders who hold shares in "street name" (i.e., those stockholders whose shares are held of record by a broker, bank or other nominee) should contact their broker, bank or nominee to ensure that their shares are voted.

If any YMTX stockholder does not receive the Proxy Statement, such stockholder should (i) confirm his or her Proxy Statement’s status with his or her broker or (ii) contact Bob Marese of MacKenzie Partners at [email protected] or John Bryan of MacKenzie Partners at [email protected]. Banks and brokers can place a collect call to Bob Marese at 212-929-5405 or John Bryan at 212-929-5735.

On November 10, 2022 ImmunityBio, Inc. (NASDAQ: IBRX),– NEJM Evidence reported that has published results from the QUILT 3.032 trial studying N-803 plus BCG in adults with NMIBC CIS with or without Ta/T1 papillary disease (Press release, ImmunityBio, NOV 10, 2022, View Source [SID1234623729]). These positive data form the basis of ImmunityBio’s BLA for BCG-unresponsive NMIBC CIS, which the FDA accepted for review in July 2022.

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The published results demonstrate that in patients with BCG-unresponsive NMIBC CIS and papillary disease, BCG plus N-803 (referred to as NAI) CRs were achieved with a persistence of effect with 90% probability of avoiding cystectomies in responders, a life-changing procedure of removing the bladder, and 100% bladder cancer-specific survival at 24 months. This investigational therapy represents an important clinical benefit addressing an unmet need of avoiding a cystectomy in this high-risk bladder cancer population.

"The peer review and publication of data in NEJM Evidence highlights the significance of the positive results of the QUILT 3.032 trial in patients with BCG-unresponsive NMIBC," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We’re targeting the 10th most commonly diagnosed cancer and the one with the highest lifetime treatment costs per patient as a result of the prolonged course of the disease and the need for repeated surgical and treatment intervention. These data further our understanding of N-803’s unique role in potentially boosting the proliferation of natural killer and T cells while synergistically enhancing BCG efficacy."

Patients with intermediate or high-risk NMIBC typically receive a treatment of transurethral resection of the bladder tumor (TURBT) followed by BCG intravesical instillation. However, cancer will recur in 30% to 40% of patients with NMIBC despite adequate treatment with BCG. Moreover, even among those in whom a complete response is achieved with BCG, up to 50% see their cancer return.

Treatment options for BCG-unresponsive NMIBC patients are limited. Pembrolizumab was approved by the FDA for this indication in 2020, based on findings from the KEYNOTE-057 study in which the CR rate in NMIBC CIS patients was 41% with a median response duration of 16.2 months. The combination of N-803 plus BCG produced both a higher CR rate and more durable responses.

In patients who received intravesical N-803 plus BCG (cohort A), a CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months 95% CI 59.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan–Meier–estimated probability of avoiding cystectomy and of disease-specific survival was 89.2% and 100%, respectively.

In patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received N-803 plus BCG (cohort B), the Kaplan–Meier–estimated disease-free survival (DFS) rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]).

Most adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%) and comparable to adverse events associated with BCG alone.

About the QUILT 3.032 Trial

In this phase 2/3, open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical N-803 plus BCG (cohort A) or N-803 alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received N-803 plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival, and overall survival were secondary end points for cohort A.

The results of this phase 2/3 study are currently being reviewed by the FDA, and a decision from the FDA regarding approval for use of the biologics N-803 plus BCG in adults with BCG-unresponsive NMIBC CIS is expected on May 23, 2023.

ImmunityBio’s IL-15 superagonist N-803

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 (generic name nogapendekin alfa inbakicept or NAI) is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 has been studied in more than 700 patients in multiple phase 1 and 2 trials in both liquid and solid tumors. In addition to the study in NMIBC, it is currently being studied in trials for pancreatic cancer, non-small-cell lung cancer, non-Hodgkin’s lymphoma, and HIV.

N-803 has received both Breakthrough Therapy and Fast Track designations by the FDA for the treatment of BCG-unresponsive NMIBC CIS, as well as Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC CIS. However, it is important to note such designations may not lead to a faster development process or regulatory review and may not increase the likelihood that a product candidate will receive approval. Seminal patents covering intravesical administration of BCG and N-803 were issued (US 11,173,191 B2 and US 9,925,247 B2) providing term coverage until 2035.

On November 10, 2022 Inventiva (Euronext Paris and Nasdaq: IVA) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of patients with non-alcoholic steatohepatitis ("NASH") and other diseases with significant unmet medical needs, reported its cash position as of September 30, 2022 and its revenues for the first nine months of 2022 (Press release, Inventiva Pharma, NOV 10, 2022, View Source [SID1234623728]).

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Cash Position

As of September 30, 2022, Inventiva’s cash position stood at €72.6 million, compared to €87.2 million as
of June 30, 2022 and €95.4 million as of December 31, 2021.

Net cash used in operating activities amounted to €40.0 million for the first nine months of 2022 compared to
€31.6 million for the same period in 2021. R&D expenses, mainly driven by the development of lanifibranor in NASH, were up 27% compared to the same period in 2021. This significant increase was driven mostly by the costs associated with the NATiV3 Phase III clinical trial of lanifibranor in NASH including a full nine months of operation for the U.S. affiliate and, to a lesser extent, with the Legend Phase IIa combination trial with lanifibranor and empagliflozin in patients with NASH and type 2 diabetes.

Cash flow from operating activities was also positively impacted in the first half of 2022 by the €4 million milestone payment from AbbVie in January 2022 following the inclusion of the first patient in the Phase IIb clinical trial with cedirogant (formerly ABBV-157) in adult patients with moderate to severe chronic plaque psoriasis, though this trial has since been discontinued by AbbVie3 as previously disclosed, and the 2021 French Research tax credit ("CIR") for €3.6 million received in April 2022.

Net cash generated from investing activities for the first nine months of 2022 amounted to €0,7 million, compared to (€1.2) million net cash consumed for the same period in 2021.

Net cash generated from financing activities for the first nine months of 2022 amounted to €13.1 million compared to €23.9 million in the same period in 2021, mainly driven by the proceeds of €9.3 million (gross proceeds) raised through the Company’s At-The-Market Program on June 15, 2022, and three loan agreements with a syndicate of French banks for a total amount of €5.3 million. One of the loans was contracted as part of a French state-guaranteed loan facility ("Prêt Garanti par l’Etat" or "PGE") with Bpifrance, and the two others obtained as part of a French state stimulus economic plan ("Prêts Participatifs Relance" or "PPR") granted by Crédit Agricole Champagne-Bourgogne and Société Générale.

In the third quarter of 2022, the Company recorded a positive exchange rate effect on cash and cash equivalents of €3.5 million for the nine-month period ending September 30, 2022, versus €1.5 million for the same period in 2021, due to the strengthening of USD versus Euro.

Considering its current R&D and clinical development programs, and additional financial resources that may originate from funding activities, the Company estimates that its existing cash, cash equivalents and short-term deposits including the $12,6 million received from Sino Biopharm on November 4th and the €25 million from the EIB credit first tranche facility4 should allow the Company to fund its operations through Q4 2023.

Revenues

The Company’s revenues for the first nine months of 2022 amounted to €0.1 million, as compared to €0.2 million for the same period in 2021. The Company’s development agreement with Sino Biopharm was executed on September 21, 2022 as previously announced and the $12.6 million upfront payment was received on November 4, 2022.

Next expected key milestones

Publication of the topline results of the investigator-initiated study with lanifibranor in patients with Non-Alcoholic Fatty Liver Disease ("NAFLD") and T2D – planned for the first quarter of 2023
Publication of the topline results of the Phase IIa LEGEND of lanifibranor in combination with empagliflozin in patients with NASH and T2D – planned for the second half of 2023
Last Patient First Visit of the Phase III NATiV3 clinical trial evaluating lanifibranor in NASH – targeted for the second half of 2023
Upcoming investor conference participation

Jefferies 2022 London Healthcare Conference – November 15-17 – London
B Riley’s Cardiometabolic Health Mini Symposium – November 28 – Virtual
Degroof Petercam’s Healthcare Conference 2023 – January 24-27 – Virtual
Guggenheim Health Altitudes Summit 2023 – March 13-16 – Telluride, Colorado
Upcoming scientific conference participation

6th Obesity and NASH Drug Development Summit – November 29 through December 1, Boston, MA
MOSAIC Conference – December 5-6, Washington, DC
Next financial results publication

Full-Year 2022 Revenues and cash position: Tuesday, February 14, 2022 (after U.S. market close).

On November 10, 2022 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 and differentiated mechanisms of action for cancer and other serious diseases, reported financial results and business updates for the third quarter of 2022 (Press release, Molecular Templates, NOV 10, 2022, View Source [SID1234623727]).

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"We are excited with the progress we continue to make across all our clinical and pre-clinical programs. We have now seen evidence of monotherapy clinical activity with MT-6402, MT-5111, and MT-0169 in heavily pretreated relapsed/refractory patients — in both solid and hematological cancer settings — demonstrating the broad potential utility of this novel scaffold," said Eric Poma, PhD., Chief Executive and Chief Scientific Officer of Molecular Templates. "We look forward to providing further updates on our MT-6402, MT-5111, and MT-0169 programs throughout 2023 and look forward to our anticipated IND submission for MT-8421 all while we continue to advance our development of additional ETB candidates targeting TROP2, TIGIT, and BCMA."

Company Highlights and Upcoming Milestones

Corporate

MTEM expects to provide periodic updates on MT-6402, MT-5111, MT-8421, and MT-0169 throughout 2023.
Dose escalation continues with MT-6402 with dose dependent pharmacodynamic (PD) effects observed. One patient in cohort 1 (16 mcg/kg) with non-small cell lung cancer (NSCLC) and osseous metastases demonstrated tumor regression. This patient is the only patient treated thus far with high tumor PD-L1 expression and HLA-A*02/ CMV+.
MT-5111 has declared Maximum Tolerated Dose (MTD) at 23 mcg/kg with a dose limiting toxicity (DLT) of grade 3 rash. The HER2-positive breast cancer (BC) dose expansion cohort (DEC) continues to enroll patients at a dose of 10 mcg/kg. Three of five evaluable BC patients treated at 10 mcg/kg have had prolonged Stable Disease for 40, 22, and 22 weeks, respectively. One of the patients treated for 22 weeks has experienced a 43% reduction in mediastinal lymphadenopathy and a halt in the growth of her pulmonary lesions. Overall, the patient has had a 14% reduction in index lesions. This patient has been previously treated with multiple HER2-targeting therapies including trastuzumab, pertuzumab, trastuzumab emtasine, lapatinib, trastuzumab deruxtecan, and tucatinib.
MT-0169 completed the 5 mcg/kg dose escalation cohort (N=4) without any cardiac adverse events (AEs) or DLTs and is enrolling at 10 mcg/kg. One patient with IgA myeloma treated at 5 mcg/kg has had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative and marked improvement of hemoglobin to normal values, demonstrating at least a Partial Response. A PET scan is pending to determine if the patient is in a Complete Response.
Of the over 80 patients treated across MTEM’s three clinical programs to date, there has been no instance of capillary leak syndrome (CLS). One patient treated at 63 mcg/kg with MT-6402 showed a grade 2 decrease in albumin that may potentially represent a subclinical manifestation of CLS.
All toxicities seen to date appear to be target-mediated and unrelated to the underlying scaffold.
ETB Technology

ETBs represent a novel platform with unique biology for therapeutic development in oncology. ETBs have the target specificity of antibodies, can force their own internalization, even against non-internalizing receptors, and can induce tumor cell death through the novel mechanism of enzymatic and irreversible ribosomal destruction. Because of this unique biology, ETBs to targets like HER2 and CD38 have the potential to drive clinical benefit in patients that have progressed after all available therapeutics. ETBs also represent a unique approach to immuno-oncology. Unlike current approaches to PD-L1 that only block the steric interaction of PD-1 and PD-L1, MT-6402, MTEM’s ETB targeting PD-L1, is designed to directly kill PD-L1+ tumors cells, destroy immune cells that inhibit T-cell function and propagate tumor growth, and alter the immunophenotype of tumor cells.

MT-6402 (PD-L1 ETB with Antigen Seeding Technology)

The Phase 1 study of MT-6402 is a multi-center, open-label, dose escalation and dose expansion trial. Patients with confirmed PD-L1 expressing tumors or confirmed PD-L1 expression in the TME are eligible for enrollment, irrespective of HLA genotype or CMV status.
As of November 2022, 19 patients with relapsed/refractory tumors that express PD-L1 have been treated across four dose cohorts: 16 mcg/kg (n=6), 24 mcg/kg (n=6), 32 mcg/kg (n=4), and 42 mcg/kg (n=3). One DLT of grade 2 rash was observed in cohort 2 whereas no DLTs were reported in cohorts 1, 3 and 4. Enrollment continues in cohort 5 at 63 mcg/kg.
One patient in cohort 1 (16 mcg/kg) with NSCLC demonstrated tumor regression of osseous metastases. This patient is the only patient treated thus far with high tumor PD-L1 expression and who is also HLA-A*02/ CMV+.
MTEM continues to observe PD effects not seen with PD-L1 antibodies and consistent with the dismantling of the TME including PD-L1+ immune cell depletion and T cell activation, as well as cytokine changes in TNF-α, IL-2, and vascular endothelial growth factor (VEGF) in all dose escalation cohorts evaluated to date. The extent and timing of these PD effects appear dose-dependent with higher dose levels showing more rapid and profound PD effects, including MDSC depletion and T cell activation. These effects were seen across the majority of patients irrespective of HLA genotype or level of tumor or immune cell PD-L1 staining.
Treatment-related AEs including immune related AEs have been largely restricted to grade 1-2.
MT-5111 (HER2 ETB)

As of November 2022, the Phase 1 study of MT-5111 has enrolled 48 patients across 10 dose escalation cohorts ranging from 0.5 mcg/kg to 23 mcg/kg. One DLT of grade 3 acneiform rash was observed at 23 mcg/kg, which improved to grade 1 with topical steroids, and the patient continued treatment at the same dose. 23 mcg/kg has been declared the MTD.
Serum concentration of MT-5111 showed predictable and dose-proportional increasing exposure starting at 6.75 mcg/kg doses and higher.
The HER2-positive BC DEC continues to enroll patients at a dose of 10 mcg/kg. Six patients have been treated, three of whom for 40, 22, and 22 weeks, respectively, at 10 mcg/kg.
One of the patients treated for 22 weeks came on study with two nodal lesions and two non-nodal necrotic pulmonary lesions. The patient has seen a continued reduction in her nodal lesions while on therapy with a 43% reduction in mediastinal lymphadenopathy and a halt in the growth of her pulmonary lesions. Overall, the patient has had a 14% reduction in index lesions. This patient has been previously treated with multiple HER2-targeting therapies including trastuzumab, pertuzumab, trastuzumab emtasine, lapatinib, trastuzumab deruxtecan, and tucatinib. The next monotherapy cohort for BC patients is planned at 17 mcg/kg.
No clinically significant cardiac AEs have been observed at any dose; grade 1 hs-troponin elevations have been observed at various doses.
MT-0169 (CD38 ETB)

The Phase 1 study in patients with relapsed/refractory multiple myeloma (MM) or non-Hodgkin’s lymphoma explores MT-0169 at doses lower than the initial dose of 50 mcg/kg to reduce the risk of AEs and to enable patients to continue MT-0169 therapy for a longer duration that may drive tumor benefit.
The 5 mcg/kg cohort completed recruitment (N=4) and analysis with no related AEs higher than grade 1. CD38+ Natural Killer (NK) cell depletion was observed in cycle 1 and in cycle 2 for patients continuing therapy. Nadir levels of NK cells were delayed and lower in magnitude than observed at 50 mcg/kg. Enrollment at 10 mcg/kg has commenced.
One patient with IgA myeloma treated at 5 mcg/kg has had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative and marked improvement of hemoglobin to normal values, demonstrating at least a Partial Response. A PET scan is pending to determine if the patient is in a Complete Response.
Research and Development

Preclinical data from MTEM’s MT-8421 program targeting CTLA-4 was featured in an abstract at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting held November 8-12, 2022, in Boston, Massachusetts. Clinical studies for MT-8421 are expected to commence in mid-2023.
MTEM continues to expand its unique approach to immuno-oncology targets with lead optimization ongoing for several targets.
Lead optimization continues on ETBs targeting TROP-2 incorporating Antigen Seeding Technology, a TIGIT-targeting ETB and BCMA.
Upcoming Conferences

MTEM will present four posters (736, 764, 817, and 1379) and provide an in-person R&D Day presentation at the SITC (Free SITC Whitepaper) annual meeting, Friday, November 11, 2022, 11:30am – 12:30pm ET. SITC (Free SITC Whitepaper) posters can be accessed via MTEM’s corporate website. The webcast can be accessed here.
MTEM will present a fireside chat at the virtual ISI HealthCONx Conference, Wednesday, November 30, 2022, at 9:15am ET. The webcast will be live-streamed and can be accessed here.
MTEM will present at the 2022 San Antonio Breast Cancer Symposium (SABCS) taking place December 6 – December 10, 2022, in San Antonio, Texas.
MTEM will participate at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s 64th annual meeting taking place December 10 – 13, 2022 in New Orleans, Louisiana. One-on-one meetings may be scheduled directly with MTEM.
Financial Results

The net loss attributable to common shareholders for the third quarter of 2022 was $24.6 million, or $0.44 per basic and diluted share. This compares with a net loss attributable to common shareholders of $30.4 million, or $0.54 per basic and diluted share, for the same period in 2021.

Revenues for the third quarter of 2022 were $4.2 million, compared to $2.4 million for the same period in 2021. Revenues for the third quarter of 2022 were comprised of revenues from collaborative research and development agreements with Bristol Myers Squibb.

Total research and development expenses for the third quarter of 2022 were $22.0 million, compared with $22.9 million for the same period in 2021. Total general and administrative expenses for the third quarter of 2022 were $5.9 million, compared with $9.0 million for the same period in 2021.

As of September 30, 2022, MTEM’s cash and investments totaled $79.4 million.

For more details on MTEM’s financial results for the third quarter 2022, refer to Form 10-Q filed with the SEC.