Futibatinib

BBI-355 POTENTIATE clinical trial ongoing with initiatives implemented to expedite enrollment in combination cohorts; initial proof-of-concept data now expected in the second half of 2025 BBI-825 STARMAP clinical trial ongoing with initial proof-of-concept data expected in the second half of 2025 ECHO ecDNA diagnostic analytically validated and IRB-approved for use as a clinical trial assay in BBI-355 POTENTIATE trial Streamlined operations expected to extend operating runway into the fourth quarter of 2026 SAN DIEGO, Aug. 12, 2024 (GLOBE NEWSWIRE) -- Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, today provided business updates for the company’s top strategic priorities and reported financial results for the second quarter of 2024. “At Boundless, we’re on a bold mission to pioneer a new category of cancer treatment for patients with oncogene amplified cancer who are in dire need of new therapeutic options,” said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. “In the second quarter of 2024, we continued to advance our first clinical-stage ecDTx, BBI-355, began dosing patients with our second ecDTx, BBI-825, and completed the analytical validation and received IRB approval of our novel ecDNA diagnostic, ECHO, for deployment as a clinical trial assay in our BBI-355 POTENTIATE trial. Though we have made progress toward our goals, the number of patients enrolled thus far in the combination cohorts of the BBI-355 POTENTIATE trial is lower than originally projected. While we implement measures to accelerate enrollment, we have chosen to scale back our early discovery efforts and streamline our operations to extend our runway and help ensure we have the necessary capital for our core ecDTx programs. Moving forward, we believe we are well-positioned to move our lead programs through initial clinical proof-of-concept data readouts and remain steadfast in advancing this innovative approach for patients with high unmet need.” Strategic Priorities for Core Programs Boundless Bio has outlined its core portfolio priorities to support the achievement of potential near-term catalysts and long-term patient impact. Through 2025, the company’s core strategic priorities remain: Executing the ongoing Phase 1/2 POTENTIATE (Precision Oncology Trial Evaluating Novel Therapeutic Interrupting Amplifications Tied to ecDNA) clinical trial of its lead ecDNA directed therapeutic candidate (ecDTx), BBI-355, a novel, oral CHK1 inhibitor, to generate initial proof-of-concept in solid tumor cancer patients with driver oncogene amplifications;Executing the ongoing Phase 1/2 STARMAP (Study Targeting Acquired Resistance: MAPK Amplifications) clinical trial of its second ecDTx, BBI-825, a novel, oral RNR inhibitor, to generate initial proof-of-concept in colorectal cancer patients with BRAFV600E or KRASG12C mutations and resistance oncogene amplifications;Advancing the company’s third ecDTx program, directed to a novel, previously undrugged kinesin target essential for ecDNA segregation, into IND-enabling studies; andDeploying its proprietary ecDNA diagnostic in the clinic to identify ecDNA+ patients who are most likely to benefit from its ecDTx therapeutics. In alignment with its strategic priorities, Boundless Bio has narrowed its discovery research work and, as a result, modestly reduced its workforce. The company believes the combination of these operational efficiencies and its cash, cash equivalents, and short-term investments of $179.3 million as of June 30, 2024, provides an operating runway into the fourth quarter of 2026. BBI-355, a novel, oral, potent, selective CHK1 inhibitor targeting replication stress for cancer patients with driver oncogene amplifications The company presented preclinical and clinical pharmacodynamic data on BBI-355 at the American Association for Cancer Research (AACR) Annual Meeting in April 2024.Enrollment is progressing in the Phase 1/2 POTENTIATE clinical trial evaluating BBI-355 as a single agent and in combination with targeted therapies in patients with locally advanced or metastatic solid tumors with oncogene amplifications.To date, no new safety signals have been observed, and there has been no evidence of combinatorial toxicity in the dose escalation cohorts evaluating BBI-355 in combination with either the EGFR inhibitor erlotinib or the FGFR inhibitor futibatinib.The initial pace of enrollment in the combination cohorts has been slower than anticipated. The company has recently implemented multiple initiatives to help accelerate enrollment, including engaging with next-generation sequencing vendors to identify patients, adding new clinical sites in the US, and preparing for the initiation of ex-US sites.Based on its current projections, the company now anticipates reporting initial clinical proof-of-concept data from POTENTIATE in the second half of 2025. BBI-825, a novel, oral, potent, selective RNR inhibitor targeting ecDNA assembly and repair for cancer patients with resistance oncogene amplifications In April 2024, the company announced the first patient had been dosed with BBI-825 in the Phase 1/2 STARMAP clinical trial.Multiple dose levels have been completed in the single-agent, dose-escalation portion of the STARMAP clinical trial and, to date, BBI-825 has demonstrated oral bioavailability and has been generally well-tolerated. Initial clinical proof-of-concept data from the trial are expected in the second half of 2025. ecDTx 3, a novel kinesin program involved in ecDNA segregation The company’s third ecDTx program, directed to a previously undrugged kinesin target essential for ecDNA segregation whose inhibition is synthetic lethal to ecDNA-enabled cancer cells, is currently advancing through lead optimization. ECHO, a proprietary diagnostic for detection of ecDNA amplified oncogenes The company’s proprietary ecDNA diagnostic, referred to as ECHO (ecDNA Harboring Oncogenes), is designed to detect ecDNA in patient tumor specimens. ECHO was previously determined by the FDA to be a non-significant risk device for use as a clinical trial assay (CTA) in the BBI-355 POTENTIATE trial.ECHO has now been analytically validated and institutional review board (IRB)-approved for use as a CTA in the BBI-355 POTENTIATE trial. Second Quarter 2024 Financial Results Cash Position: Cash, cash equivalents, and short-term investments totaled $179.3 million as of June 30, 2024.R&D Expenses: Research and development (R&D) expenses were $14.7 million for the second quarter of 2024 compared to $11.1 million for the same period in 2023.G&A Expenses: General and administrative (G&A) expenses were $4.7 million for the second quarter of 2024 compared to $2.9 million for the same period in 2023.Net Loss: Net loss totaled $17.0 million for the second quarter of 2024 compared to $12.4 million for the same period in 2023. About BBI-355 Boundless Bio’s lead ecDTx, BBI-355, is a novel, oral, selective small molecule inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial (NCT05827614) in cancer patients with oncogene amplifications. CHK1 is a master regulator of cells’ response to replication stress (RS). RS is elevated in cancer cells with oncogene amplification, including on ecDNA, and, because of this, represents a key vulnerability of those cells. BBI-355 was designed to exploit the elevated RS in ecDNA-enabled oncogene amplified cancer cells by disrupting proper CHK1 function in regulating RS and thereby facilitating catastrophic RS to preferentially kill cancer cells relative to healthy cells. About BBI-825 Boundless Bio’s second ecDTx, BBI-825, is a novel, oral, selective small molecule inhibitor of ribonucleotide reductase (RNR) being studied in the ongoing, first-in-human, Phase 1/2 STARMAP clinical trial (NCT06299761) in colorectal cancer patients with BRAFV600E or KRASG12C mutations and resistance gene amplifications. In preclinical studies, BBI-825 demonstrated low double digit nanomolar RNR inhibition and tumor growth inhibition, including regressions, in both the prevention and treatment of amplification-mediated resistance in mitogen-activated protein kinase (MAPK) pathway-activated tumors. RNR is the rate-limiting enzyme responsible for cellular de novo synthesis of deoxynucleotide triphosphates (dNTPs), the building blocks of DNA, and is essential to the assembly and repair of ecDNA. BBI-825 was shown to dysregulate ecDNA-reliant cancer cell dNTP pools, deplete ecDNA, and was synthetic lethal in multiple oncogene amplified preclinical cancer models. About Boundless Bio Boundless Bio is a clinical-stage oncology company dedicated to unlocking a new paradigm in cancer therapeutics to address the significant unmet need of patients with oncogene amplified tumors by targeting extrachromosomal DNA (ecDNA), a root cause of oncogene amplification observed in more than 14% of cancer patients. Boundless Bio is developing the first ecDNA-directed therapeutic candidates (ecDTx), BBI-355, which is an oral inhibitor of checkpoint kinase 1 (CHK1) being evaluated in a Phase 1/2 clinical trial in cancer patients with oncogene amplifications. Boundless Bio’s second ecDTx, BBI-825, is an oral inhibitor of ribonucleotide reductase (RNR) being evaluated in a Phase 1/2 clinical trial in colorectal cancer patients with BRAFV600E or KRASG12C mutations and resistance gene amplifications. Leveraging its Spyglass platform, Boundless Bio has an additional program (ecDTx 3) advancing through preclinical development and discovery. Boundless Bio is headquartered in San Diego, CA. For more information, visit www.boundlessbio.com. Follow us on LinkedIn and X. Forward-Looking Statements Boundless Bio cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include but are not limited to: the potential to achieve catalysts and long-term patient impact; the potential to expedite enrollment in the POTENTIATE trial; the timing of expected data readouts; the impact on our cash runway of our streamlining efforts and the sufficiency of our cash position and such efforts to fund operations and initial clinical proof-of-concept data readouts; and the potential safety and therapeutic benefits of our ecDTx in treating patients with oncogene amplified cancers. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: we are early in our development efforts and our approach to discover and develop ecDTx directed against ecDNA in oncogene amplified cancers is novel and unproven; results from preclinical studies or early clinical trials not necessarily being predictive of future results; potential delays in the commencement, enrollment, data readouts or completion of clinical trials or preclinical studies; our dependence on third parties in connection with clinical trials, preclinical studies, ecDNA diagnostic development, and manufacturing; unfavorable results from clinical trials or preclinical studies; we may expend our limited resources to pursue a particular ecDTx and fail to capitalize on ecDTx with greater development or commercial potential; unexpected adverse side effects or inadequate efficacy of our ecDTx that may limit their development, regulatory approval, and/or commercialization; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; regulatory developments in the United States and foreign countries; efforts to streamline operations may not produce the efficiencies expected; we may use our capital resources sooner than we expect; and other risks described in our filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our quarterly report on Form 10-Q for the quarter ended June 30, 2024 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investor Contacts: Ben Flaum, Boundless Biobflaum@boundlessbio.com Renee Leck, THRUST Strategic Communications renee@thrustsc.com Media Contact: Dan Budwick, 1ABDan@1abmedia.com BOUNDLESS BIO, INC. Condensed Financial Information(Unaudited) Condensed Statements of Operations Data:Three months ended June 30 Six months ended June 30 (In thousands, except per share amounts)2024 2023 2024 2023 Operating expenses: Research and development$14,735 $11,075 $27,864 $20,577 General and administrative 4,656 2,885 8,410 5,470 Total operating expenses 19,391 13,960 36,274 26,047 Loss from operations (19,391) (13,960) (36,274) (26,047)Other income, net: Interest income 2,382 1,551 3,803 1,914 Other income, net 33 11 65 16 Total other income, net 2,415 1,562 3,868 1,930 Net loss$(16,976) $(12,398) $(32,406) $(24,117)Net loss per share, basic and diluted$(0.77) $(10.28) $(2.78) $(20.18)Weighted-average shares used in calculation 22,023 1,206 11,641 1,195 Condensed Balance Sheet Data: June 30, December 31, (In thousands) 2024 2023 Cash, cash equivalents, and short-term investments $179,290 $120,752 Total assets $188,203 $129,894 Total liabilities $8,957 $9,359 Convertible preferred stock $- $247,617 Accumulated deficit $(168,515) $(136,109)Total stockholders' equity (deficit) $179,246 $(127,082)Working capital (1) $174,175 $114,845 __________ (1) We define working capital as current assets less current liabilities.

BBI-355 Phase 1/2 POTENTIATE clinical trial ongoing; initiated targeted therapy combinations in patients with tumors with EGFR or FGFR oncogene amplifications First patient dosed in Phase 1/2 STARMAP clinical trial of BBI-825 in patients with tumors with resistance gene amplifications Completed $100 million IPO; pro forma cash position of approximately $200 million supports both BBI-355 and BBI-825 through preliminary clinical proof of concept SAN DIEGO--(BUSINESS WIRE)-- Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, today announced financial results for the first quarter of 2024 and highlighted recent progress. “It has been an exciting quarter at Boundless Bio. The Phase 1/2 POTENTIATE trial of BBI-355, our potentially best-in-class, oral, selective CHK1 inhibitor, advanced into initial combination therapy modules evaluating BBI-355 together with an EGFR inhibitor or an FGFR inhibitor in patients with tumors harboring EGFR or FGFR oncogene amplifications, respectively. We also dosed the first patient with our second ecDNA-directed therapy (ecDTx), BBI-825, a first-in-class, oral, selective RNR inhibitor, which marks the company’s rapid growth and transition into a multi-asset, clinical-stage oncology company” said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. “With the completion of our recent IPO, we have the capital to take the next steps toward delivering on the promise of our ecDTx, a potential new vertical in cancer therapeutics.” Recent Highlights BBI-355, a novel CHK1 inhibitor and the first ecDTx in development Patient enrollment is ongoing in Part 1 of the Phase 1/2 POTENTIATE (Precision Oncology Trial Evaluating Novel Therapeutic Interrupting Amplifications Tied to ecDNA) trial, which evaluates BBI-355 as a single agent in patients with locally advanced or metastatic solid tumors with oncogene amplifications. Initiated dose escalation in Part 2 of the Phase 1/2 POTENTIATE trial, which evaluates BBI-355 in combination with the EGFR inhibitor erlotinib and BBI-355 in combination with the FGFR inhibitor futibatinib in patients with tumors harboring EGFR or FGFR oncogene amplifications, respectively, to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of each combination regimen. Presented preliminary preclinical and clinical pharmacodynamic data on BBI-355 at the American Association for Cancer Research (AACR) Annual Meeting 2024. Findings further support the development of BBI-355 as a differentiated single agent and combination treatment approach for oncogene amplified cancers. BBI-825, a novel, selective RNR inhibitor targeting ecDNA assembly and repair Dosed the first patient in the STARMAP (Study Targeting Acquired Resistance: MAPK Amplifications) trial, a first-in-human, Phase 1/2 study of BBI-825 as a single agent and in combination with select targeted cancer therapies, for patients with locally advanced or metastatic cancer with resistance gene amplifications. First Quarter 2024 Financial Highlights Cash Position: Cash, cash equivalents, and short-term investments totaled $104.9 million as of March 31, 2024. In addition, Boundless Bio completed its IPO in early April 2024 in which it sold 6,250,000 shares of its common stock for gross proceeds of $100.0 million. Boundless Bio expects its current cash position to fund operations into the second half of 2026 and through key clinical data milestones. R&D Expenses: Research and development (R&D) expenses were $13.1 million for the first quarter of 2024, compared to $9.5 million for the same period in 2023. The increase in R&D expenses was primarily due to a $1.8 million increase in the direct program costs for BBI-355, BBI-825, and other development programs, a $0.5 million increase in personnel-related costs resulting from an increase in headcount and salary increases, $0.3 million of additional stock-based compensation, and a $1.0 million increase in third-party services and other miscellaneous R&D costs. G&A Expenses: General and administrative (G&A) expenses were $3.8 million for the first quarter of 2024, compared to $2.6 million for the same period in 2023. The increase in G&A expenses was primarily due to a $0.3 million increase in personnel-related costs due to an increase in headcount and salary increases, $0.5 million of additional stock-based compensation, an increase in professional service fees of $0.2 million, and a $0.2 million increase in other G&A costs. Net Loss: Net loss totaled $15.4 million and $11.7 million for the first quarters of 2024 and 2023, respectively, with non-cash stock-based compensation expense of $1.3 million and $0.6 million for the first quarters of 2024 and 2023, respectively. About BBI-355 Boundless Bio’s lead ecDNA-directed therapy (ecDTx), BBI-355, is a novel, oral, selective small molecule inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial (NCT05827614) in patients with oncogene amplified cancers. CHK1 is a master regulator of cells’ response to replication stress (RS). RS is elevated in ecDNA-enabled oncogene amplified cancer cells and, because of this, represents a key vulnerability of those cells. BBI-355 was designed to exploit the elevated RS in ecDNA-enabled oncogene amplified cancer cells by disrupting proper CHK1 function in regulating RS and thereby facilitating catastrophic RS to preferentially kill cancer cells relative to healthy cells. About BBI-825 Boundless Bio’s second ecDTx, BBI-825, is a novel, oral, selective small molecule inhibitor of ribonucleotide reductase (RNR) being studied in the ongoing, first-in-human, Phase 1/2 STARMAP clinical trial (NCT06299761) in cancer patients with resistance gene amplifications. In preclinical studies, BBI-825 demonstrated low double digit nanomolar RNR inhibition and tumor growth inhibition, including regressions, in both the prevention and treatment of amplification-mediated resistance in mitogen-activated protein kinase (MAPK) pathway-activated tumors. RNR is the rate-limiting enzyme responsible for cellular de novo synthesis of deoxynucleotide triphosphates (dNTPs), the building blocks of DNA, and is essential to the assembly and repair of ecDNA. BBI-825 was shown to dysregulate ecDNA-reliant cancer cell dNTP pools, deplete ecDNA, and was synthetic lethal in multiple oncogene amplified preclinical cancer models. About Boundless Bio Boundless Bio is a clinical-stage oncology company dedicated to unlocking a new paradigm in cancer therapeutics to address the significant unmet need of patients with oncogene amplified tumors by targeting extrachromosomal DNA (ecDNA), a root cause of oncogene amplification observed in more than 14% of cancer patients. Boundless Bio is developing the first ecDNA-directed therapy (ecDTx), BBI-355, which is an oral inhibitor of checkpoint kinase 1 (CHK1) being evaluated in a Phase 1/2 clinical trial in patients with oncogene amplified cancers. Boundless Bio’s second ecDTx, BBI-825, is an oral inhibitor of ribonucleotide reductase (RNR) being evaluated in a Phase 1/2 clinical trial in cancer patients with resistance gene amplifications. Leveraging its Spyglass platform, Boundless Bio has additional programs advancing through preclinical development and discovery. Boundless Bio is headquartered in San Diego, CA. For more information, visit . Follow us on LinkedIn and X. Forward-Looking Statements Boundless Bio cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include but are not limited to: the sufficiency of our cash position to fund operations and milestones; and the potential therapeutic benefits of our ecDTx in treating patients with oncogene amplified cancers. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: we are early in our development efforts and our approach to discover and develop ecDTx directed against ecDNA in oncogene amplified cancers is novel and unproven; results from preclinical studies or early clinical trials not necessarily being predictive of future results; potential delays in the commencement, enrollment, data readouts or completion of clinical trials or preclinical studies; our dependence on third parties in connection with clinical trials, preclinical studies, ecDNA diagnostic development, and manufacturing; unfavorable results from clinical trials or preclinical studies; unexpected adverse side effects or inadequate efficacy of our ecDTx that may limit their development, regulatory approval, and/or commercialization; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; regulatory developments in the United States and foreign countries; we may use our capital resources sooner than we expect; and other risks described in our filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our quarterly report on Form 10-Q for the quarter ended March 31, 2024 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. BOUNDLESS BIO, INC. Condensed Statements of Operations (unaudited) (In thousands, except per share amounts) Three Months Ended March 31, 2024 2023 Operating expenses: Research and development $ 13,129 $ 9,503 General and administrative 3,754 2,584 Total operating expenses 16,883 12,087 Loss from operations (16,883 ) (12,087 ) Other income (expense): Interest income 1,421 395 Other income (expense) 32 (27 ) Total other income, net 1,453 368 Net loss $ (15,430 ) $ (11,719 ) Net loss per share, basic and diluted $ (12.27 ) $ (9.91 ) Shares used in calculation 1,258 1,183 BOUNDLESS BIO, INC. Condensed Balance Sheets (In thousands, except par value data) March 31, 2024 December 31, 2023 (unaudited) Assets Current assets Cash and cash equivalents $ 25,143 $ 23,706 Short-term investments 79,737 97,046 Prepaid expenses and other current assets 7,281 3,452 Total current assets 112,161 124,204 Property and equipment, net 2,418 2,573 Right-of-use asset, net 1,385 2,002 Restricted cash 560 560 Other assets 553 555 Total assets $ 117,077 $ 129,894 Liabilities, convertible preferred stock, and stockholders’ deficit Current liabilities Accounts payable and accrued liabilities $ 8,182 $ 4,266 Accrued compensation 939 2,898 Lease liabilities, current portion 1,523 2,195 Total current liabilities 10,644 9,359 Convertible preferred stock 247,617 247,617 Stockholders’ equity: Common stock, $0.0001 par value — — Additional paid-in-capital 10,376 8,987 Accumulated other comprehensive income / (loss) (21 ) 40 Accumulated deficit (151,539 ) (136,109 ) Total stockholders’ deficit (141,184 ) (127,082 ) Total liabilities, convertible preferred stock, and stockholders’ deficit $ 117,077 $ 129,894 View source version on businesswire.com: Contacts James Lee, Boundless Bio jlee@boundlessbio.com Investors THRUST Strategic Communications Renee Leck renee@thrustsc.com Media 1AB Dan Budwick dan@1abmedia.com Source: Boundless Bio View this news release online at: