MCT1

LEXINGTON, Mass.--( BUSINESS WIRE )--Cyteir Therapeutics, Inc. (“Cyteir”) (Nasdaq: CYT), a clinical stage oncology company, today presented results from a Phase 1 study with CYT-0851 in combination with capecitabine or gemcitabine in a poster titled “Phase 1 Results of CYT-0851, a Monocarboxylate Transporter (MCT) Inhibitor, in Combination with Capecitabine or Gemcitabine in Advanced Solid Tumors” (Abstract: 3099, Poster: 297) at the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois. “We are encouraged by the preliminary data from the Phase 1 dose escalation study with CYT-0851 in combination with capecitabine and gemcitabine and are pleased that the safety profile of CYT-0851 continues to be generally tolerable even when combined with these standard chemotherapy agents,” said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. “The Cyteir team is diligently executing on the clinical development of CYT-0851 as a potential combination therapy, and we look forward to sharing preliminary data for all patients in these cohorts mid-year.” Phase 1 Study Objectives The primary objective of the ongoing Phase 1 study is to determine the recommended Phase 2 dose and maximum tolerated dose of CYT-0851 in combination with capecitabine or gemcitabine. Key secondary objectives include evaluation of safety and tolerability, determination of the pharmacokinetic parameters, optimal dosing regimen for each combination and characterization of preliminary anti-tumor activity of the combinations. Phase 1 Study Preliminary Findings The data presented in the poster are the first report of preliminary results of an ongoing study. As of the May 1, 2023 data cutoff, 22 patients were enrolled in the capecitabine cohort across four dose-escalation cohorts from 100 mg to 400 mg once daily dose and 13 patients were enrolled in the gemcitabine cohort across three dose-escalation cohorts from 100 mg to 300 mg once daily dose. Fourteen patients in the capecitabine arm were response evaluable and eight patients in the gemcitabine arm were response evaluable. The recommended Phase 2 dose in the capecitabine combination is 400 mg once a day with no dose limiting toxicities observed. The maximum tolerated dose in the combination of CYT-0851 with capecitabine was not identified. The dose escalation of CYT-0851 in combination with gemcitabine is ongoing and the study has cleared the 200 mg dose. Combination of CYT-0851 with capecitabine Seven ovarian cancer patients and seven pancreatic cancer patients were response evaluable with RECIST measurements available. There was one partial response in an ovarian cancer patient with treatment ongoing in cycle 12 and nine patients had stable disease (five pancreatic cancer patients and four ovarian cancer patients). The overall disease control rate in the capecitabine combination was 71.4%. Combination of CYT-0851 with gemcitabine Five sarcoma patients, two pancreatic cancer patients and one ovarian cancer patient were response evaluable. There was one confirmed partial response in a sarcoma patient at month two and six patients with stable disease (three sarcoma patients, two pancreatic patients and one ovarian cancer patient). The overall disease control rate was 87.5%. Safety: To date, CYT-0851 has exhibited a generally well tolerated safety profile without unanticipated toxicities observed at clinically active doses, and without exacerbation of the expected toxicity from the chemotherapy combination partners. In the capecitabine cohort, 45.5% of patients reported adverse events with 9.1% being grade 3/4. The most common treatment-related adverse events were fatigue (27.3%), decreased appetite (13.6%) and nausea (13.6%). In the gemcitabine cohort, 69.2% of patients reported adverse events with 46.2% being grade 3/4. The most common treatment-related adverse events were fatigue (38.5%), anemia (23.1%) and neutropenia (23.1%). No dose-limiting toxicities were observed in any patients treated with the combination of CYT-0851 and capecitabine. In the CYT-0851 plus gemcitabine combination cohorts, one patient at the 300 mg level had dose-limiting hyperglycemia with starvation ketoacidosis that resolved upon treatment interruption and has not recurred upon rechallenge at a lower dose. No treatment related deaths have been reported, and no patients experienced a treatment related adverse event that led to discontinuation of CYT-0851. About Cyteir Therapeutics, Inc. Cyteir is a clinical-stage oncology company that is focused on the development of CYT-0851, an oral investigational drug that inhibits monocarboxylate transporters. Cyteir’s current priority in CYT-0851 development is in combination with capecitabine and gemcitabine in a Phase 1/2 clinical study, including patients with advanced ovarian cancer. Follow Cyteir on social media: LinkedIn and Twitter and at www.cyteir.com . Forward-Looking Statements This press release contains “forward-looking statements” about Cyteir’s strategy, future plans, and prospects, including statements regarding the development of CYT-0851, regulatory strategy and path for CYT-0851, and the expected timing and reporting of data for CYT-0851. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “plan,” “potential,” “project,” “seek,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to: that Cyteir’s clinical trials may fail to demonstrate adequately the safety and efficacy of CYT-0851; that preclinical testing of CYT-0851 may not be predictive of the results or success of clinical trials; that the clinical development of CYT-0851 may be delayed or otherwise take longer and/or cost more than planned; that Cyteir may be unable to initiate, enroll or complete clinical development of CYT-0851; that preliminary data may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data; that the continuing global outbreak of COVID-19 (including any resurgences or variants) may result in development or manufacturing delays, supply shortages, or shortages of qualified healthcare personnel; that synthetic lethality, as an emerging class of precision medicine targets, could result in negative perceptions of the efficacy, safety or tolerability of this class of targets, which could adversely affect our ability to conduct our business, advance our drug candidates or obtain regulatory approvals; and that Cyteir’s compounds may not receive regulatory approvals or become commercially successful products. These and other risks and uncertainties are identified under the heading “Risk Factors” in Cyteir’s most recent Annual Report on Form 10-K and other filings Cyteir has made and may make with the Securities and Exchange Commission ("SEC") in the future, available on the SEC's website at www.sec.gov . The forward-looking statements contained in this press release are based on management's current views, plans, estimates, assumptions, and projections with respect to future events, and Cyteir does not undertake and specifically disclaims any obligation to update any forward-looking statements.

- Enrollment continuing in trials with CYT-0851 in combination with capecitabine or gemcitabine with data expected in mid-2023 - Ended first quarter of 2023 with approximately $137.2 million in cash LEXINGTON, Mass.--(BUSINESS WIRE)-- Cyteir Therapeutics, Inc. (“Cyteir”) (Nasdaq: CYT), a clinical stage oncology company, today reported financial results for the first quarter ended March 31, 2023 and provided an update on recent operational highlights. “We have made encouraging progress enrolling patients in the CYT-0851 Phase 1 combination trial with capecitabine and gemcitabine, while maintaining our strong financial discipline,” said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. “We look forward to sharing preliminary data on the Phase 1 combination cohorts with CYT-0851 in mid-year.” Recent Updates to the CYT-0851 Clinical Program Enrollment in the Phase 1 trial with CYT-0851 in combination with capecitabine in advanced ovarian cancer continues at the 400mg dose of CYT-0851, which was determined to be the recommended Phase 2 dose in the capecitabine combination. Preliminary data on the combination with capecitabine are expected to be disclosed in mid-2023. Enrollment in the Phase 1 dose escalation cohorts of CYT-0851 in combination with gemcitabine in solid tumors continues. A maximum tolerated dose and/or recommended Phase 2 dose of CYT-0851 in combination with gemcitabine is expected to be determined and preliminary results to be disclosed in mid-2023. A poster of preliminary results of monotherapy and combination data with CYT-0851 will be presented at the American Society of Clinical Oncology during the Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology poster session on June 3, 2023 at 8:00am. Poster title: Phase 1 results of CYT-0851, a monocarboxylate transporter (MCT) inhibitor, in combination with capecitabine (cape) or gemcitabine (gem) in advanced solid tumors. Abstract: 3099, Poster Bd #: 297 Recent Business Updates Cyteir is pursuing out-licensing of its preclinical DNA polymerase theta (POLθ or POLQ) inhibitor program. First Quarter 2023 Financial Results Cash and cash equivalents: Cash and cash equivalents as of March 31, 2023 were $137.2 million, which are expected to fund planned operations into 2026. Research and development (R&D) expenses: R&D expenses were $9.3 million for the first quarter of 2023 versus $10.1 million for the same period in 2022. The year-over-year decrease in R&D spending was due primarily to a decrease in costs related to our MCT inhibitor program, which includes research activities and ongoing clinical trial costs, partially offset by an increase in personnel severance-related costs. General and administrative (G&A) expenses: G&A expenses were $4.1 million for the first quarter of 2023 compared to $4.0 million for the same period in 2022. The year-over-year increase in G&A expenses was primarily due to an increase in personnel severance-related costs, partially offset by a decrease in insurance and state taxes. Net loss: Net loss was $12.5 million, or $0.35 per share, in the first quarter of 2023 compared to $14.1 million, or $0.40 per share, for the same period in 2022. About Cyteir Therapeutics, Inc. Cyteir is a clinical-stage oncology company that is focused on the development of CYT-0851, an oral investigational drug that inhibits monocarboxylate transporters. Cyteir’s current priority in CYT-0851 development is in combination with capecitabine and gemcitabine in a Phase 1/2 clinical study, including patients with advanced ovarian cancer. Follow Cyteir on social media: LinkedIn and Twitter and at . Forward-Looking Statements This press release contains “forward-looking statements” about Cyteir’s strategy, future plans, and prospects, including statements regarding the development of Cyteir’s compounds and potential expansion opportunities, regulatory strategy, and path for Cyteir’s compounds, the expected timing and reporting of results of Cyteir’s preclinical and clinical studies, and Cyteir’s expected cash runway. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “plan,” “potential,” “project,” “seek,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include: the benefits and potential impact of our portfolio prioritization; expected timing to receive clinical data from current ongoing clinical studies; expected cost savings from our prioritization and reduction in force; and our expected extended cash runway. Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to: that Cyteir’s clinical trials may fail to demonstrate adequately the safety and efficacy of CYT-0851; that preclinical testing of CYT-0851 may not be predictive of the results or success of clinical trials; that the clinical development of CYT-0851 may be delayed or otherwise take longer and/or cost more than planned; that Cyteir may be unable to initiate, enroll or complete clinical development of CYT-0851; that the continuing global outbreak of COVID-19 (including any resurgences or variants) may result in development or manufacturing delays, supply shortages, or shortages of qualified healthcare personnel; that synthetic lethality, as an emerging class of precision medicine targets, could result in negative perceptions of the efficacy, safety or tolerability of this class of targets, which could adversely affect our ability to conduct our business, advance our drug candidates or obtain regulatory approvals; and that Cyteir’s compounds may not receive regulatory approvals or become commercially successful products. These and other risks and uncertainties are identified under the heading “Risk Factors” in Cyteir’s most recent Annual Report on Form 10-K and other filings Cyteir has made and may make with the Securities and Exchange Commission ("SEC") in the future, available on the SEC's website at . The forward-looking statements contained in this press release are based on management's current views, plans, estimates, assumptions, and projections with respect to future events, and Cyteir does not undertake and specifically disclaims any obligation to update any forward-looking statements. Cyteir Therapeutics Inc Condensed consolidated statements of operations (in thousands, except share and per share amounts) (unaudited) Three Months Ended March 31, 2023 2022 Operating expenses: Research and development $ 9,312 $ 10,088 General and administrative 4,110 4,043 Total operating expenses 13,422 14,131 Loss from operations (13,422 ) (14,131 ) Other income (expense): Interest income 1,543 29 Loss on disposal of property and equipment (925 ) - Gain on lease terminations and modification 318 - Total other income (expense) 936 29 Net loss $ (12,486 ) $ (14,102 ) Net loss per share—basic and diluted $ (0.35 ) $ (0.40 ) Weighted-average common stock outstanding—basic and diluted 35,587,806 35,241,251 Research and development expenses for both the first quarter-ended March 31, 2023 and 2022 include stock-based compensation expense of $0.4 million. General and administrative expenses for the first quarter-ended March 31, 2023 include stock-based compensation expense of $0.6 million compared to $0.8 million in the corresponding periods of 2022. Cyteir Therapeutics Inc Condensed consolidated balance sheets (in thousands, except share and per share amounts) (unaudited) March 31, December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 137,204 $ 147,120 Prepaid expenses and other current assets 1,190 2,089 Total current assets $ 138,394 $ 149,209 Property and equipment, net 323 1,699 Other assets 259 2,324 Total assets $ 138,976 $ 153,232 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 674 $ 1,128 Accrued expenses and other current liabilities 3,287 4,187 Total current liabilities $ 3,961 $ 5,315 Other long term liabilities 39 1,631 Total liabilities $ 4,000 $ 6,946 Commitments and contingencies (Note 10) Stockholders’ equity: Preferred stock, $0.001 par value: 40,000,000 shares authorized as of March 31, 2023 and December 31, 2022, respectively; no shares issued and outstanding as of March 31, 2023 and December 31, 2022 - - Common stock, $0.001 par value: 280,000,000 shares authorized; 35,658,429 and 35,575,694 shares issued as of March 31, 2023 and December 31, 2022, respectively; 35,624,127 and 35,516,249 shares outstanding as of March 31, 2023 and December 31, 2022, respectively 35 35 Additional paid-in capital 285,541 284,365 Accumulated deficit (150,600 ) (138,114 ) Total stockholders’ equity 134,976 146,286 Total liabilities and stockholders’ equity $ 138,976 $ 153,232

People with liver disease caused by eating too much sugar and fat could be at increased risk of developing serious neurological conditions like depression or dementia. In a study examining the link between non-alcoholic fatty liver disease (NAFLD) and brain dysfunction, scientists at the Roger Williams Institute of Hepatology, affiliated to King's College London and the University of Lausanne, found an accumulation of fat in the liver causes a decrease in oxygen to the brain and inflammation to brain tissue -- both of which have been proven to lead to the onset of severe brain diseases. NAFLD affects approximately 25% of the population and more than 80% of morbidly obese people. Several studies have reported the negative effects of an unhealthy diet and obesity can have on brain function however this is believed to be the first study that clearly links NAFLD with brain deterioration and identifies a potential therapeutic target. The research, conducted in collaboration with Inserm (the French National Institute of Health and Medical Research) and the University of Poitiers in France, involved feeding two different diets to mice. Half of the mice consumed a diet with no more than 10% fat in their calorie intake, while the other half's calorie intake contained 55% fat; intended to resemble a diet of processed foods and sugary drinks. After 16 weeks researchers conducted a series of tests to compare the effects of these diets on the body and more specifically, on the liver and the brain. They found that all mice consuming the higher levels of fat were considered obese, and developed NAFLD, insulin resistance and brain dysfunction. The study which was funded by the University of Lausanne and Foundation for Liver Research also showed that the brain of mice with NAFLD suffered from lower oxygen levels. This is because the disease affects the number and thickness of the brain blood vessels, which deliver less oxygen to the tissue, but also due to specific cells consuming more oxygen while the brain is becoming inflamed. These mice were also more anxious and showed signs of depression. By comparison, the mice consuming the healthy diet did not develop NAFLD or insulin resistance, they behaved normally, and their brain was completely healthy. "It is very concerning to see the effect that fat accumulation in the liver can have on the brain, especially because it often starts off mild and can exist silently for many years without people knowing they have it," said lead author Dr Anna Hadjihambi, sub-team lead in the Liver-Brain Axis group at the Roger Williams Institute of Hepatology and honorary lecturer at King's College London. To try and combat the dangerous effect that NAFLD has on the brain, the scientists bred mice with lower levels of a whole-body protein known as Monocarboxylate Transporter 1 (MCT1) -- a protein specialised in the transport of energy substrates used by various cells for their normal function. When these mice were fed the same unhealthy fat- and sugar-rich diet as those in the initial experiment, they had no fat accumulation in the liver and exhibited no sign of brain dysfunction -- they were protected from both ailments. "Identifying MCT1 as a key element in the development of both NAFLD and its associated brain dysfunction opens interesting perspectives," said Professor Luc Pellerin, director of the Inserm U1313 research unit at the University of Poitiers in France and senior researcher in the study. "It highlights potential mechanisms at play within the liver-brain axis and points to a possible therapeutic target." Dr Hadjihambi added: "This research emphasises that cutting down the amount of sugar and fat in our diets is not only important for tackling obesity, but also for protecting the liver to maintain brain health and minimise the risk of developing conditions like depression and dementia during ageing, when our brain becomes even more fragile.