Coffin-Lowry Syndrome

AUSTIN, Texas, March 04, 2024 (GLOBE NEWSWIRE) -- 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, today provided an update on its programs. Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, “ETBs represent a new approach to oncology drug development that continue to show unique biology and monotherapy activity in heavily pre-treated patients. We are particularly excited about the monotherapy activity observed with our MT-6402 program in patients with head and neck cancer.” Company Highlights Continued single agent activity observed with MT-6402 particularly in heavily pre-treated patients with head and neck cancer who had progressed on multiple prior therapies including checkpoint antibodies. The first dose of 32 mcg/kg has been cleared with no grade 3 or grade 4 drug-related toxicities in the phase I study for MT-8421 targeting CTLA-4-expressing regulatory T-cells (“Tregs”) in the tumor microenvironment. Unique pharmacodynamic effects demonstrating potent Treg clearance and IL-2 increases were observed at the first dose level. Enrollment in the second dose cohort (48 mcg/kg) is on-going. MTEM intends to initiate a study of MT-0169 in CD38+ acute leukemias in collaboration with MD Anderson Cancer Center. Preclinical activities related to Bristol Myers Squibb collaboration are on-going. MT-6402 (PD-L1 ETB) The Part A dose escalation of the phase I study for MT-6402 has been completed with no Grade 4 or Grade 5 drug-related adverse events observed to date. In the Part A dose escalation, 10 patients with head and neck squamous cell cancer (HNSCC) were treated at doses of 63, 83, or 100 mcg/kg. Two of these patients were not evaluable for the cycle 1 dose-limiting toxicity (“DLT”) period or for efficacy because of early progression and came off study after receiving only one or two doses of MT-6402, respectively. Of the remaining eight head and neck cancer patients, the best responses observed were as follows: three had a partial response (“PR”) (two unconfirmed) and a fourth patient had evidence of tumor regression. All four patients had progressed on their previous therapies after multiple lines of treatment including checkpoint antibodies. Additional details on each of these participant’s clinical pro response to the investigational treatment are provided below. 1 patient with a PD-L1 TPS of 2% who had progressed after chemotherapy, radiation therapy, and pembrolizumab had a confirmed PR with 70% tumor reduction and remains on study in cycle 18 (1 cycle = 4 weeks). 1 patient with a PD-L1 CPS of 10% who had progressed after three previous lines of therapy, including progression on Ipi/Nivo within 4 months, showed deepening tumor reduction over time of 3%, 9%, and 15% at the end of cycles 2, 4, and 6, respectively. At the end of cycle 8, the patient had an unconfirmed PR with a 37% reduction in tumor size. The patient remains on study in cycle 9. 1 patient with a PD-L1 CPS of 5% who had progressed after six prior lines of therapy and was refractory to pembrolizumab received 2 doses of MT-6402 before coming off treatment due to the treating physician’s concerns around an asymptomatic grade 1 high sensitivity troponin elevation and hyponatremia related to excessive alcohol intake. The patient discontinued treatment, but a subsequent CT scan assessed by an external radiology review showed that the patient had a 36% tumor reduction (an unconfirmed PR). 1 patient with a PD-L1 CPS of 10% with pre-existing cardiac risk factors of hypertension, hyperlipidemia, and hypercholesterolemia received three doses of MT-6402 before presenting with asymptomatic grade 1 high sensitivity troponin elevation and dosing was held. A CT scan showed a 13% reduction in tumor size, but disease progression occurred during treatment interruption and patient discontinued at the end of cycle 6. The three other HNSCC patients enrolled in the Part A dose escalation had stable disease of 6, 4, and 2 months, respectively, before disease progression or study discontinuation. One patient progressed at the end of cycle 2. Of these 8 patients, only one patient (the patient with stable disease through 6 cycles) had a PD-L1 tumor proportion score (“TPS”) greater than 50%. “We are very excited to see objective responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need,” said Eric Poma. “Current checkpoint monotherapy in I/O-naïve head and neck cancer patients has a ~15% response rate. Here, in patients who have progressed on checkpoint therapy, we believe we are seeing preliminary evidence of monotherapy activity of long duration and in patients refractory to checkpoint therapy. The partial responses observed to date were in patients with low PD-L1 expression and also showed concomitant increases in cytokines associated with T-cell activation that are not seen with other checkpoint therapies. We believe these data demonstrate a new and potentially best-in-class approach to targeting the PD-1-PD-L1 axis.” “MT-6402 appears generally well-tolerated at the 63 and 83 mcg/kg doses with no Grade 4 or Grade 5 adverse events and no instances of CLS seen at any dose,” said Dr. Maurizio Voi, Chief Medical Officer of Molecular Templates. “The irAE pro MT-6402, including the asymptomatic high sensitivity troponin elevations, appears to be consistent with that seen with other checkpoint therapies.” The Part B dose expansion portion of the phase I study in patients with high PD-L1 is ongoing. MT-8421 (CTLA-4 ETB) MT-8421, along with MT-6402, represent our unique approach to immuno-oncology based on dismantling the TME through the elimination of immunosuppressive cells in the TME. MT-8421 is designed to potently destroy CTLA4+ Tregs via enzymatic ribosome destruction but does not have activity against low CTLA-4 expressing peripheral Tregs. Three patients were dosed in the first cohort of the phase I study at 32 mcg/kg. No grade 3 or grade 4 drug-related adverse events were observed. Two patients have stable disease and remain on study at cycle 4 and cycle 2, respectively (1 cycle = 4 weeks). One patient had disease progression at the end of cycle 2. The two patients in stable disease showed peripheral depletion of Tregs and significant elevations in IL-2 while on therapy. Enrollment is on-going in the second cohort of 48 mcg/kg for the phase I study of MT-8421. MT-0169 (CD38 ETB) MT-0169 is 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). A phase 1 study in patients with relapsed or refractory multiple myeloma was closed on Dec 2023 due to slow patient enrollment in the wake of multiple new approvals in myeloma. This study enrolled 14 patients and no drug-related Grade 4 or 5 adverse events have been observed. One patient with IgA myeloma who was quad-refractory was treated at 5 mcg/kg and had a stringent Complete Response for 16 cycles (1 cycle = 4 weeks) before discontinuing treatment for progression of disease. MTEM plans on initiating an investigator sponsored trial with MD Anderson Cancer Center to evaluate MT-0169 in relapsed or refractory CD38+ AML patients. Research and Collaboration MTEM continues to make progress in the drug discovery collaboration with Bristol Myers Squibb. Previously Announced Process to Explore Strategic Alternatives Previously, Molecular Templates announced that it has retained Stifel, Nicolaus & Company to assist Molecular Templates in initiating a comprehensive evaluation of strategic alternatives, including, but not limited to, potential financing/recapitalization opportunities, the sale of all, or part, of the company, or a merger, or other strategic transactions. A timetable for completion of this strategic review process has not been set, and there can be no assurance that this strategic review will result in any completed transaction. About Molecular Templates Molecular Templates is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted biologic therapeutics. Our proprietary drug platform technology, known as engineered toxin bodies, or ETBs, leverages the resident biology of a genetically engineered form of Shiga-like Toxin A subunit to create novel therapies with potent and differentiated mechanisms of action for cancer. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Molecular Templates disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. All statements, other than statements of historical facts, included in this press release, including, but not limited to those regarding strategy, future operations, the Company’s ability to execute on its objectives, prospects, plans, future clinical development of the Company’s product candidates, any implication that the preliminary results, interim results, or the results of earlier clinical trials or ongoing clinical trials will be representative of the results of future or later clinical trials or final results, the potential benefits, safety or efficacy and any evaluations or judgements regarding the Company’s product candidates, [the results of any strategic process which are inherently uncertain at the present time] and future execution of corporate goals. In addition, when or if used in this press release, the words “may,” “could,” “should,” “continue”, “anticipate,” “potential”, “believe,” “estimate,” “appears”, “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Molecular Templates may identify forward-looking statements. Forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors including, but not limited to the following: the continued availability of financing on commercially reasonable terms, whether Molecular Templates’ cash resources will be sufficient to fund its continuing operations; the results of MTEM’s ongoing clinical studies and its collaboration activities with BMS, the ability to effectively operate MTEM, and those risks identified under the heading “Risk Factors” in Molecular Templates’ filings with the Securities and Exchange Commission (the “SEC”), including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and any subsequent reports filed with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Molecular Templates specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise. Contacts: Grace Kim grace.kim@mtem.com Photos accompanying this announcement are available at: Monotherapy Activity with MT-6402 in Low-PD-L1 Relapsed/Refractory SCHNN Patients (N=8) Monotherapy Activity with MT-6402 in Low-PD-L1 Relapsed/Refractory SCHNN Patients (N=8) MT-8421 Induces Unique Pharmacodynamic Effects MT-8421 Induces Unique Pharmacodynamic Effects

Data spans eleven presentations across both solid tumors and hematologic malignancies, providing added understanding of the potential benefit these therapies bring to patients ORSERDU data reinforce its key role in the treatment of ER+, HER2- advanced or metastatic breast cancer (mBC) tumors that harbor ESR1 mutations, while showing initial data from combination trials ELZONRIS presentation includes updated real-world data from patients with Blastic Plasmacytoid Dendritic Cell Neoplasm FLORENCE, Italy & NEW YORK--(BUSINESS WIRE)-- The Menarini Group ("Menarini"), a leading Italian pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, announced today that they will present new data related to ORSERDU® (elacestrant) and ELZONRIS® (tagraxofusp-erzs) in two upcoming congresses. This press release features multimedia. View the full release here: ORSERDU, a once-daily oral endocrine monotherapy, for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy, was approved by the U.S. Food and Drug Administration in January 2023 under its priority review and fast track designation. In September 2023, ORSERDU was approved by the European Commission. Updated data, including a spotlight discussion on additional biomarker and clinical subgroup analyses from the Phase 3 EMERALD trial, along with new safety updates evaluating elacestrant in multiple combination settings, will be presented at the San Antonio Breast Cancer Symposium (SABCS), December 5-9, 2023. ELZONRIS was approved by the FDA in December 2018 for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adult and pediatric patients two years and older, in both treatment-naïve and previously-treated populations. In January 2021, ELZONRIS was approved by the European Commission. Updated data, including an oral presentation of updated real-world results in treatment-naïve patients with BPDCN demonstrating durable outcomes and a manageable safety pro to prolonged survival, will be presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, December 9-12, 2023. “The breadth of data on our novel oncology therapies, spanning solid tumors and hematologic malignancies, underscore our commitment to addressing significant unmet medical needs in difficult-to-treat cancers,” said Elcin Barker Ergun, CEO of the Menarini Group. “At Menarini Stemline, we are dedicated to driving innovation in oncology to deliver targeted therapies that bring value to people living with cancer and to the healthcare providers who care for them.” See below for full details of the Menarini Group/Stemline Therapeutics' upcoming presentations: San Antonio Breast Cancer Symposium 2023 Lead Author​ Abstract Title and ID​ Presentation Details​ Bardia, A​ Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial​ 1576519/PS17-02 December 8, 2023​ 7-8am CT Poster Spotlight Discussion Hemisfair Ballroom 1-2 Rugo, H​ ELEVATE: A phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC)​ 1576517/PO2-05-04 December 6, 2023 5-7pm CT​ Poster Halls 2-3 Ibrahim, N​ ELECTRA: An open-label, multicenter, phase 1b/2 study of elacestrant in combination with abemaciclib in patients with brain metastasis (mets) from estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer (BC) 1576518​/PO2-05-05 December 6, 2023​ 5-7pm CT​ Poster Halls 2-3 Patnaik, A​ SUMIT-ELA: Phase 1b/2 combination of cyclin-dependent kinase 7 inhibitor (CDK7i) samuraciclib and selective estrogen receptor degrader (SERD) elacestrant in advanced hormone receptor positive (HR+) breast cancer after CDK4/6i* NA/PO3-04-13 December 7, 2023 12-2pm CT​ Poster Halls 2-3 Bellet, M​ A phase 2 randomized pre-operative, window of opportunity trial investigating the effect of elacestrant with/without triptorelin in premenopausal patients with HR+/HER2- breast cancer – SOLTI-2104-PremiÈRe trial*​ 1580190/PO3-19-08 December 7, 2023​ 12-2pm CT​ Poster Halls 2-3 *Denotes investigator sponsored research or collaborative research 65th American Society of Hematology (ASH) Annual Meeting 2023 Lead Author Title and Publication Number Session Name Presentation Details Angelucci et al. Durable Outcomes with Manageable Safety Leading to Prolonged Survival with Tagraxofusp for Treatment-Naive Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm: Updated Results from a European Named Patient Program Publication Number: 547 906. Outcomes Research – Myeloid Malignancies: Real-World Treatment Patterns and Outcomes Oral Presentation December 10, 2023 12:00 PM Marriott Marquis San Diego Marina, Marriott Grand Ballroom 11-13 Minetto et al. Single Agent Tagraxofusp in Relapsed/Refractory CD123-Positive Acute Myeloid Leukemia: An Interim Analysis of Italian GIMEMA AML2020 Trial* Publication Number: 2918 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II Poster Presentation December 10, 2023 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Lane et al. Tagraxofusp in Combination with Azacitidine and Venetoclax in Newly Diagnosed CD123+ Acute Myeloid Leukemia, Expansion Cohort of a Phase 1b Multicenter Trial* Publication Number: 4277 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III Poster Presentation December 11, 2023 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Boichut et al. Analysis of tagraxofusp activity in AML-PDC as a single agent and in combination with BCL2 inhibitors* Publication Number: 2783 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II Poster Presentation December 10, 2023 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Navarro Vicente et al. Clinical Features and Treatment in Patients Diagnosed with Blastic Plasmacytoid Dendritic Cell Neoplasm: Interim Analysis from the Pethema Epidemiologic Registry (EPI-BLAS study)* Publication Number: 4234 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster III Poster Presentation December 11, 2023 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H *Denotes investigator sponsored research or collaborative research About the EMERALD Phase 3 Study (NCT03778931) The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/mBC patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator's choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC. About ORSERDU® (elacestrant) U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is approved by the U.S. Food & Drug Administration (FDA) for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Full prescribing information for the U.S. can be found at Important Safety Information, ORSERDU® Warning and Precautions Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid pro to starting and periodically while taking ORSERDU. Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose. Adverse Reactions Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each). The most common adverse reactions (>10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite (15%), diarrhea (13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%). Drug interactions Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU. Use in specific populations Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose. Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B). The safety and effectiveness of ORSERDU in pediatric patients have not been established. To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or . Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE (NCT05563220); ELECTRA (NCT05386108); and ELCIN (NCT05596409). Elacestrant is also being evaluated in early breast cancer disease. About ELZONRIS® (tagraxofusp-erzs) U.S. Indication: ELZONRIS (tagraxofusp-erzs) is a prescription medicine used to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients 2 years and older. Full prescribing information for the U.S. can be found at IMPORTANT SAFETY INFORMATION, ELZONRIS® Boxed WARNING: CAPILLARY LEAK SYNDROME Capillary Leak Syndrome (CLS) which may be life-threatening or fatal, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of CLS and take actions as recommended. Warnings and Precautions Capillary Leak Syndrome Capillary leak syndrome (CLS), including life-threatening and fatal cases, has been reported among patients treated with ELZONRIS. In patients receiving ELZONRIS in clinical trials, the overall incidence of CLS was 53% (65/122), including Grade 1 or 2 in 43% (52/122) of patients, Grade 3 in 7% (8/122) of patients, Grade 4 in 1% (1/122) of patients, and four fatalities (3%). The median time to onset was 4 days (range - 1 to 46 days), and all but 5 patients experienced an event in Cycle 1. Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is greater than or equal to 3.2 g/dL. During treatment with ELZONRIS, monitor serum albumin levels prior to the initiation of each dose of ELZONRIS and as indicated clinically thereafter, and assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema, including pulmonary edema, hypotension or hemodynamic instability. Hypersensitivity Reactions ELZONRIS can cause severe hypersensitivity reactions. In patients receiving ELZONRIS in clinical trials, hypersensitivity reactions were reported in 43% (53/122) of patients treated with ELZONRIS and were Grade ≥ 3 in 7% (9/122). Manifestations of hypersensitivity reported in ≥ 5% of patients include rash, pruritus, and stomatitis. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur. Hepatotoxicity Treatment with ELZONRIS was associated with elevations in liver enzymes. In patients receiving ELZONRIS in clinical trials, elevations in ALT occurred in 79% (96/122) and elevations in AST occurred in 76% (93/122). Grade 3 ALT elevations were reported in 26% (32/122) of patients. Grade 3 AST elevations were reported in 30% (36/122) and Grade 4 AST elevations were reported in 3% (4/122) of patients. Elevated liver enzymes occurred in the majority of patients in Cycle 1 and were reversible following dose interruption. Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Withhold ELZONRIS temporarily if the transaminases rise to greater than 5 times the upper limit of normal and resume treatment upon normalization or when resolved. Adverse Reactions Most common adverse reactions (incidence ≥ 30%) are capillary leak syndrome, nausea, fatigue, pyrexia, peripheral edema, and weight increase. Most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, and sodium, and increases in glucose, ALT and AST. Please see full Prescribing Information, including Boxed WARNING. To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or contact the FDA at 1-800-FDA-1088 or . About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit . About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. (“Stemline”) a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the U.S. and E.U., an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the U.S. and E.U. to date. Stemline also commercializes NEXPOVIO® (selinexor) in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. View source version on businesswire.com: Contacts Media The Menarini Group Valeria Speroni Cardi Email: pressoffice@menarini.com Stemline Therapeutics, Inc. Cheya Pope Email: cpope@menarinistemline.com Source: The Menarini Group and its subsidiary Stemline Therapeutics, Inc. View this news release online at:

AUSTIN, Texas, Nov. 13, 2023 (GLOBE NEWSWIRE) -- 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, today reported financial results and business updates for the third quarter of 2023. Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, “ETBs represent a new approach to oncology drug development that continue to show unique biology and monotherapy activity in heavily pre-treated patients. We expect to see substantial additional data across all three of our clinical programs with updates throughout this year and into 2024.” Company Highlights Initiation of expansion study with MT-6402 (PD-L1) exploring 63 and 83 mcg/kg doses; compelling early evidence of monotherapy activity in patients with relapsed or refractory Head and Neck cancer observed at the 63 and 83 mcg/kg doses observedFirst patient dosed in phase I study for MT-8421 targeting CTLA-4-expressing regulatory T-cells (“Tregs”) in the tumor microenvironment (“TME”) for elimination without affecting peripheral TregsMT-0169 (CD38): The company is in the process of declaring the recommended doses that will be further investigated in CD38+ malignancies. Clinical data for each program continues to demonstrate 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 observedNo instances of capillary leak syndrome (“CLS”) or other manifestations of innate immunity have been observed to date with any next-generation ETBFocus on preclinical activities related to Bristol Myers Squibb collaboration moves forward MT-6402 (PD-L1 ETB) The Part A dose escalation of the phase I for MT-6402 has been completed with no Grade 4 or Grade 5 drug-related adverse events having been observed to date. In the Part A dose escalation, 10 patients with head and neck cancer were treated at doses of 63, 83, or 100 mcg/kg. Two of these patients were not evaluable for the cycle 1 dose-limiting toxicity (“DLT”) period because of early progression and came off study after receiving only one or two doses of MT-6402, respectively. Of the remaining eight head and neck cancer patients, the best responses observed were as follows: two had a partial response (one unconfirmed), and a third patient had evidence of tumor regression. All three patients had progressed after multiple lines of treatment including checkpoint therapy. The unconfirmed partial response was in a patient who was pembrolizumab-refractory. Three other patients had stable disease of 6, 4, and 2 months, respectively, before disease progression or discontinuation. A fourth patient remains in stable disease at cycle 5. One patient progressed at the end of cycle 2. Of these 8 patients, only one patient (the patient with stable disease through 6 cycles) had a PD-L1 tumor proportion score (“TPS”) greater than 50%. “We are very excited to see responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need,” said Eric Poma. “The TME in head and neck tumors is typically rich with immunosuppressive cells, but current checkpoint monotherapy in I/O-naïve head and neck patients has a ~15% response rate. Here, in patients who have progressed on checkpoint therapy, we believe we are seeing evidence of monotherapy activity of long duration and monotherapy activity in a patient refractory to checkpoint therapy. The responses observed to date were in patients with CPS <20% and showed concomitant increases in cytokines associated with T-cell activation that are not seen with other checkpoint therapies. We believe these data demonstrate a new and potentially best-in-class approach to targeting the PD-1-PD-L1 axis.” “MT-6402 appears generally well-tolerated at the 63 and 83 mcg/kg doses with no Grade 4 or Grade 5 adverse events and no instances of CLS seen at any dose,” said Dr. Maurizio Voi, Chief Medical Officer of Molecular Templates. “The irAE profile of MT-6402 appears to be consistent with that seen with other checkpoint therapies.” The Part B dose expansion is ongoing, with three patients currently on treatment but not yet evaluable for efficacy. The 63 and 83 mcg/kg doses will be studied in the expansion cohort in patients with >50% tumor expression of PD-L1, allowing for the potential of direct tumor cell-kill. Additionally, in patients with the HLA-A*02 haplotype and who are CMV+, the antigen seeding mechanism of MT-6402 may be engaged. MT-8421 (CTLA-4 ETB) MT-8421, along with MT-6402, represent our unique approach to immuno-oncology based on dismantling the TME through, and the elimination of, immunosuppressive cells in the TME.MT-8421 is designed to potently destroy CTLA4+ Tregs via enzymatic ribosome destruction but does not have activity against low CTLA-4 expressing peripheral Tregs.Clinical sites are open and enrollment has commenced on this program. 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).MT-0169 will continue to be studied in CD38 hematological malignancies. No adverse events ≥ Grade 3 have been observed.One patient with extra medullary IgA myeloma treated at 5 mcg/kg has had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative and resolution of uptake on bone scan of skeletal lesions demonstrating a stringent Complete Response. The patient’s disease was quad-agent refractory, including CD38-targeting antibody, proteosome inhibitor, IMiD, and a BCMA bispecific antibody.The patient continues on study in a response at cycle 16. Research and Collaboration MTEM continues to make progress in the drug discovery collaboration with Bristol Myers Squibb. Key Upcoming Milestones Accelerating enrollment across all clinical programs.Advancement of Bristol Myers Squibb research collaboration across multiple targets. Under terms of the agreement, Molecular Templates received $70M upfront and will undertake research responsibilities for the discovery of next-generation ETBs for multiple undisclosed targets.MTEM expects to provide a year-end update and periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2024. Upcoming Conferences Stifel Annual Health Care Conference Format: Live Presentation and One-on-One MeetingsDate: Wednesday, November 15, 2023Time: 10:55 am Eastern TimeLocation: Lotte New York Palace Hotel, New York, NYWebcast: The live-streamed webcast can be accessed hereMeetings: To be scheduled by contact with Stifel representative The presentation link will be archived for 90 days here in the “News and Media” section of the corporate website. Evercore ISI 6th Annual HealthCONx Conference Format: One-on-one meetingsDates: November 28 - 30, 2023Location: Kimpton Epic Hotel, Miami, FLMeetings: To be scheduled directly with Molecular Templates Financial Results The net loss attributable to common shareholders for the third quarter of 2023 was $4.2 million, or $0.82 per basic share and per diluted share. This compares with a net loss attributable to common shareholders of $24.6 million, or $6.56 per basic and diluted share, for the same period in 2022. Revenues for the third quarter of 2023 were $6.8 million, compared to $4.2 million for the same period in 2022. Revenues for the third quarter of 2023 were comprised of revenues from the collaborative research and development agreement with Bristol Myers Squibb and grant revenue from CPRIT. Total research and development expenses for the third quarter of 2023 were $7.6 million, compared with $22.0 million for the same period in 2022. Total general and administrative expenses for the third quarter of 2023 were $4.3 million, compared with $5.9 million for the same period in 2022. As of September 30, 2023, MTEM’s cash and cash equivalents totaled $15.8 million. MTEM anticipates cash runway to the end of the second quarter of 2024. About Molecular Templates Molecular Templates is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted biologic therapeutics. Our proprietary drug platform technology, known as engineered toxin bodies, or ETBs, leverages the resident biology of a genetically engineered form of Shiga-like Toxin A subunit to create novel therapies with potent and differentiated mechanisms of action for cancer. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Molecular Templates disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. All statements, other than statements of historical facts, included in this press release, including, but not limited to those regarding strategy, future operations, the Company’s ability to execute on its objectives, prospects, plans, future clinical development of the Company’s product candidates, any implication that the preliminary results or the results of earlier clinical trials will be representative of the results of future clinical trials, the potential benefits, safety or efficacy and any evaluations or judgements regarding the Company’s product candidates, and future execution of corporate goals. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Molecular Templates may identify forward-looking statements. Forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors including, but not limited to the following: the continued availability of financing on commercially reasonable terms, whether Molecular Templates’ cash resources will be sufficient to fund its continuing operations; the results of MTEM’s ongoing clinical studies and its collaboration activities with BMS, the ability to effectively operate MTEM, and those risks identified under the heading “Risk Factors” in Molecular Templates’ filings with the Securities and Exchange Commission (the “SEC”), including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and any subsequent reports filed with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Molecular Templates specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise. Contacts:Grace Kimgrace.kim@mtem.com Molecular Templates, Inc.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except share and per share data)(unaudited) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2023 2022 2023 2022 Research and development revenue$5,732 $4,240 $45,986 $17,143 Grant revenue 1,064 — 4,304 — Total revenue 6,796 4,240 50,290 17,143 Operating expenses: Research and development 7,624 21,973 40,079 64,835 General and administrative 4,309 5,934 15,306 20,120 Total operating expenses 11,933 27,907 55,385 84,955 Loss from operations 5,137 23,667 5,095 67,812 Interest and other income, net 210 307 1,030 563 Interest and other expense, net (31) (1,224) (2,615) (3,365)Gain on extinguishment of debt — — 1,795 — Change in valuation of contingent value right 881 — 1,184 — Loss on disposal of property and equipment (76) (28) (475) (29)Loss before provision for income taxes 4,153 24,612 4,176 70,643 Provision for income taxes — 26 — 26 Net loss attributable to common stockholders$4,153 $24,638 $4,176 $70,669 Net loss per share attributable to common stockholders: Basic and diluted$0.82 $6.56 $0.99 $18.82 Weighted average number of shares used in net loss per share calculations: Basic and diluted 5,092,859 3,756,658 4,206,986 3,755,178 Molecular Templates, Inc.CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands, except share and per share data) September 30, 2023 (unaudited) December 31,2022ASSETS Current assets: Cash and cash equivalents$15,811 $32,190 Marketable securities, current — 28,859 Prepaid expenses 2,999 3,459 Other current assets 3,890 3,790 Total current assets 22,700 68,298 Operating lease right-of-use assets 9,667 11,132 Property and equipment, net 8,578 14,632 Other assets 3,116 3,486 Total assets$44,061 $97,548 LIABILITIES AND STOCKHOLDERS’ EQUITY/(DEFICIT) Current liabilities: Accounts payable$2,583 $504 Accrued liabilities 3,303 8,823 Deferred revenue, current 13,210 45,573 Other current liabilities 2,416 2,182 Total current liabilities 21,512 57,082 Deferred revenue, long-term — 5,904 Long-term debt, net of current portion — 36,168 Operating lease liabilities, long term portion 10,396 12,231 Contingent value right liability 3,975 — Other liabilities 1,377 1,295 Total liabilities 37,260 112,680 Commitments and contingencies Stockholders’ equity/(deficit) Preferred stock, $0.001 par value: Authorized: 2,000,000 shares as of September 30, 2023 and December 31, 2022; Issued and outstanding: 250 shares at September 30, 2023 and December 31, 2022 — — Common stock, $0.001 par value: Authorized: 150,000,000 shares as of September 30, 2023 and December 31, 2022; Issued and outstanding: 5,374,268 shares at September 30, 2023 and 3,756,711 shares at December 31, 2022 respectively1 5 4 Additional paid-in capital1 455,739 429,698 Accumulated other comprehensive income/(loss) 1 (66)Accumulated deficit (448,944) (444,768)Total stockholders’ equity/(deficit) 6,801 (15,132)Total liabilities and stockholders’ equity/(deficit)$44,061 $97,548 1. Prior period amounts have been retrospectively adjusted for the 1-for-15 reverse stock split that was effective August 11, 2023.