Bio Path Holdings Inc (BPTH) 2024 Q3 法說會逐字稿

Good morning, and welcome to the Bio-Path Holdings Incorporated third-quarter 2024 conference call. (Operator Instructions) Please note this event is being recorded.

早上好，歡迎參加 Bio-Path Holdings Incorporated 2024 年第三季電話會議。（操作員說明）請注意此事件正在被記錄。

I would now like to turn the conference over to Will O'Connor of Stern Investor Relations. Please go ahead.

我現在想將會議轉交給斯特恩投資者關係部的威爾·奧康納 (Will O'Connor)。請繼續。

Thank you, operator. Welcome to the Bio-Path Holdings conference call and webcast to review the company's third-quarter 2024 financial results and to provide an update on recent pipeline and corporate developments. Earlier, we issued a press release, which outlines the topics we plan to discuss on today's call and that press release is available at biopathholdings.com.

謝謝你，接線生。歡迎參加 Bio-Path Holdings 電話會議和網路廣播，回顧該公司 2024 年第三季的財務業績，並提供有關最新產品線和公司發展的最新資訊。早些時候，我們發布了一份新聞稿，概述了我們計劃在今天的電話會議上討論的主題，該新聞稿可在 biopathholdings.com 上取得。

With me today from Bio-Path are President and CEO, Peter Nielsen; and Senior Vice President of Finance, Accounting, and Administration, Anthony Price.

今天與我在一起的有 Bio-Path 總裁兼執行長 Peter Nielsen；財務、會計和行政高級副總裁 Anthony Price。

Before we begin the call, I'd like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we urge you to read. Our actual results may differ materially from what is discussed on today's call.

在我們開始通話之前，我想提醒您，今天的討論將包含涉及風險和不確定性的前瞻性陳述。這些風險和不確定性在今天的新聞稿和公司最近向美國證券交易委員會提交的文件中進行了概述，我們強烈建議您閱讀這些文件。我們的實際結果可能與今天電話會議中討論的內容有重大差異。

With that, I'll now turn the call over to Bio-Path's CEO, Peter Nielsen.

現在，我將把電話轉給 Bio-Path 的執行長 Peter Nielsen。

Thanks, Will. Good morning, everyone, and thank you for joining us. As we approach the end of 2024, I look back with pride on all we have achieved. Importantly, we continue to deliver on our promise to usher in a new era of DNA-powered medicine.

謝謝，威爾。大家早安，感謝您加入我們。隨著 2024 年底的臨近，我對我們所取得的一切感到自豪。重要的是，我們將繼續兌現我們的承諾，開創 DNA 驅動醫學的新時代。

I'll begin this morning with an exciting development that expands the utility of our DNAbilize platform beyond oncology.

今天早上我將從一項令人興奮的開發開始，將我們的 DNAbilize 平台的實用性擴展到腫瘤學之外。

Last month, we announced the initiation of our clinical development program for BP-1001-A as a treatment for obesity and related metabolic diseases. This marks the first application of our DNAbilize platform for development of a noncancer application, which highlights the broad therapeutic potential of this technology.

上個月，我們宣布啟動 BP-1001-A 的臨床開發計劃，用於治療肥胖和相關代謝疾病。這標誌著我們的 DNAbilize 平台首次應用於非癌症應用的開發，凸顯了該技術的廣泛治療潛力。

BP1001-A is a modified product from prexigebersen sharing the same drug substance with enhanced nanoparticle properties. The disease pathology, leading to obesity suggests that BP-1001-A, which suppresses the adapter protein, GRB 2 has the potential to treat insulin resistance, a major contributor to obesity, Type 2 diabetes, and other related metabolic diseases.

BP1001-A 是 prexigebersen 的改良產品，具有相同的藥物成分，但具有增強的奈米顆粒特性。導致肥胖的疾病病理學表明，抑制接頭蛋白 GRB 2 的 BP-1001-A 有可能治療胰島素阻抗，而胰島素阻抗是導致肥胖、2 型糖尿病和其他相關代謝疾病的主要原因。

Based on our review of published research, we expect down regulating GRB 2 expression with BP1001-A will enhance insulin sensitivity. Preclinical studies to confirm these assumptions will kick off this quarter, and we expect these findings will provide crucial insights into the mechanism and efficacy of BP-1001-A in enhancing insulin sensitivity and reveal its therapeutic potential for obesity and Type 2 diabetes.

根據我們對已發表研究的回顧，我們預期用 BP1001-A 下調 GRB 2 表現將增強胰島素敏感性。證實這些假設的臨床前研究將於本季度啟動，我們預計這些發現將為 BP-1001-A 增強胰島素敏感性的機制和功效提供重要見解，並揭示其治療肥胖和 2 型糖尿病的潛力。

Beyond obesity, we also continue to advance a Phase 1/1b clinical trial of BP1001-A in patients with solid tumors including ovarian, endometrial, pancreatic and triple-negative breast cancer, some of the most challenging cancers to treat with today's therapeutic tool kit.

除了肥胖之外，我們也持續在實體瘤患者中推進BP1001-A 的1/1b 期臨床試驗，包括卵巢癌、子宮內膜癌、胰臟癌和三陰性乳癌，這些癌症是當今治療工具包治療中最具挑戰性的一些癌症。

This trial is being conducted at several leading cancer centers and will initially evaluate the safety in solid tumor patients. Patients diagnosed with recurrent ovarian and endometrial cancer often have poor outcomes, and it is our hope that we may provide clinical benefit for such patients.

該試驗正在幾個領先的癌症中心進行，最初將評估實體瘤患者的安全性。被診斷為復發性卵巢癌和子宮內膜癌的患者通常預後不佳，我們希望能為此類患者提供臨床益處。

We look forward to the next dose cohort completion and data readout from this study potentially early next year. Turning now to the progress we have made with our lead product candidate, prexigebersen. We continue to advance the amended Stage 2 of our Phase 2 trial in AML.

我們期待明年初完成下一個劑量隊列並讀出這項研究的數據。現在談談我們的主要候選產品 prexigebersen 所取得的進展。我們繼續推進 AML 第二階段試驗的修訂後的第二階段。

It is an open-label, two-stage multi-center study of prexigebersen in combination with decitabine and venetoclax in two cohorts of patients with previously untreated AML refractory relapsed AML. A third cohort includes the treatment of refractory relapsed AML patients who are venetoclax resistant or intolerant with the two-drug combination of prexigebersen and decitabine.

這是一項開放標籤、兩階段多中心研究，在兩組先前未經治療的 AML 難治性復發 AML 患者中，使用 prexigebersen 聯合地西他濱和 Venetoclax 進行研究。第三組包括治療對 Venetoclax 有抗藥性或不耐受 Prexigebersen 和地西他濱兩種藥物組合的難治性復發性 AML 患者。

The primary endpoint for this study will be the number of patients who achieve complete remission, which includes complete remissions with incomplete hematologic recovery and complete remission with partial hematologic recovery.

本研究的主要終點是實現完全緩解的患者數量，包括完全緩解但血液學不完全恢復和完全緩解但部分血液學恢復。

We also made considerable progress advancing our Phase 1/1b clinical trial of BP1002 in refractory relapsed AML patients. BP1002 targets the BcL-2 protein. However, BP1002 activity is based on blocking the BcL-2 messenger RNA and not the BH3 domain, which is the mechanism of treatment for the frontline drug venetoclax.

我們也在難治性復發性 AML 患者中推進 BP1002 的 1/1b 期臨床試驗，取得了相當大的進展。BP1002 標靶 BcL-2 蛋白。然而，BP1002 的活性是基於阻斷 BcL-2 信使 RNA，而不是 BH3 結構域，這是一線藥物 Venetoclax 的治療機制。

BcL-2 is responsible for driving cell survival in up to 60% of all cancers, high expression of BcL-2 and has been correlated with poor prognosis for patients diagnosed with AML. As a result, we believe that BP1002 could provide an alternative for venetoclax patients who have relapsed, including AML patients who previously received venetoclax treatments.

BcL-2 負責驅動高達 60% 的所有癌症的細胞存活，BcL-2 的高表達與 AML 患者的不良預後相關。因此，我們相信 BP1002 可以為復發的 Venetoclax 患者提供替代方案，包括先前接受 Venetoclax 治療的 AML 患者。

By targeting the key protein involved in the venetoclax treatment at the messenger RNA level, BP1002 may overcome and prevent some of the mechanisms of resistance that affect venetoclax treatment.

透過在信使 RNA 層級靶向 Venetoclax 治療中涉及的關鍵蛋白，BP1002 可以克服並預防一些影響 Venetoclax 治療的抗藥性機制。

Venetoclax has shown activity against the antiapoptotic protein BcL-2 and works by neutralizing the protein's BH3 domain. It is an improved treatment for chronic lymphocytic leukemia, or CLL patients and untreated AML patients. However, with the exception of some patients treated with allogenetic hematopoietic cell transplantation, relapse invariably incurs oftentimes due to BH3 domain mutation over time.

Venetoclax 已顯示出抗凋亡蛋白 BcL-2 的活性，並透過中和該蛋白的 BH3 結構域發揮作用。它是對慢性淋巴細胞白血病或 CLL 患者和未經治療的 AML 患者的改進治療方法。然而，除了部分接受同種異體造血細胞移植治療的患者外，由於BH3結構域隨著時間的推移發生突變，常常會導致復發。

A total of three evaluable patients for dosing cohort are scheduled to be treated with BP1002 monotherapy in a standard 3+3 design, unless there is a dose-limiting toxicity, which would require an additional 3 patients tested. The first dose cohort consisted of a starting dose of 20 milligrams per square meter, and there were no dose-limiting toxicity.

劑量組中總共三名可評估的患者計劃按照標準 3+3 設計接受 BP1002 單藥治療，除非存在劑量限制性毒性，否則需要額外測試 3 名患者。第一個劑量組的起始劑量為每平方公尺 20 毫克，且沒有劑量限制性毒性。

The approved treatment cycle is two doses per week over 4 weeks with a total of 8 doses administered over 28 days. The Phase 1b portion of the study is expected to commence after completion of BP1002 monotherapy cohorts and will assess the safety and efficacy of BP1002 in combination with decitabine in refractory relapsed AML patients.

核准的治療週期是在 4 週內每週注射兩劑，在 28 天內總共注射 8 劑。研究的 1b 期部分預計將在 BP1002 單藥治療組完成後開始，並將評估 BP1002 與地西他濱聯合治療難治性復發性 AML 患者的安全性和有效性。

After the FDA completed its review of data from the first dosing cohorts, we initiated enrollment for the third higher dosing cohort of 60 milligrams per square meter. Enrollment was completed within 6 weeks, faster than projected, which underscores the continued need for new treatment options in this vulnerable patient population.

FDA 完成對第一個劑量組數據的審查後，我們開始招募第三個更高劑量組（每平方米 60 毫克）。登記工作在 6 週內完成，比預期的要快，這凸顯了這個弱勢患者群體持續需要新的治療方案。

Finally, let's review the progress we've made with BP1003, which targets the STAT3 protein. STAT3 is a transcription factor that regulates various tumorigenic processes such as tumor proliferation, metastasis and drug resistance.

最後，讓我們回顧一下針對 STAT3 蛋白的 BP1003 所取得的進展。STAT3是一種轉錄因子，調節腫瘤增殖、轉移和抗藥性等多種致瘤過程。

It's overexpression and aberrant activation characterize many cancers including breast, lung, ovarian, liver and colon cancer. Activation of STAT3 pathway in breast and ovarian cancer cells promotes tumor initiation, migration, and taxol resistance. STAT3 also promotes 5-FU resistance in colorectal cancer cells.

它的過度表現和異常活化是許多癌症的特徵，包括乳腺癌、肺癌、卵巢癌、肝癌和結腸癌。乳癌和卵巢癌細胞中 STAT3 路徑的活化促進腫瘤發生、遷移和紫杉醇抗藥性。STAT3 也促進大腸直腸癌細胞對 5-FU 的抗藥性。

Its role in numerous malignancies made stat free a potential cancer therapeutic target. BP1003 is a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide that efficiently reduces STAT3 expression and enhances the sensitivity of breast and ovarian cancer cells to taxol in 5-FU.

它在多種惡性腫瘤中的作用使得 stat free 成為潛在的癌症治療標靶。BP1003是一種新型脂質體摻入的STAT3反義寡脫氧核苷酸，可有效降低STAT3表現並增強乳癌和卵巢癌細胞對5-FU中紫杉醇的敏感性。

In September, we announced a publication highlighting the therapeutic potential of BP1003 in a variety of cancer types in the peer-reviewed journal Biomedicines. The article describes the broad antitumor effect of BP1003 in numerous preclinical solid tumor models including breast, ovarian, and pancreatic cancer.

9 月，我們在同行評審期刊《生物醫學》上發表了一篇文章，強調了 BP1003 在多種癌症類型中的治療潛力。該文章描述了 BP1003 在多種臨床前實體瘤模型（包括乳腺癌、卵巢癌和胰腺癌）中的廣泛抗腫瘤作用。

After an extended period of testing, we have identified a method for oligo detection in trace quantities in plasma that we expect will enable us to complete final safety needed to finalize an investigational new drug or IND application for submission to the FDA. We are particularly excited to launch our first in-human validation of this cutting-edge therapy in an especially challenging cancer indication that has limited treatment options.

經過長時間的測試，我們已經確定了一種檢測血漿中微量寡核苷酸的方法，我們預計該方法將使我們能夠完成最終確定研究性新藥或向FDA 提交IND 申請所需的最終安全性。我們特別高興能夠在治療選擇有限的特別具有挑戰性的癌症適應症中啟動這種尖端療法的首次人體驗證。

With that, I'll now hand over the program to Anthony Price for a brief review of our financials along with balance sheet highlights. Anthony?

現在，我將把該計劃交給安東尼·普萊斯，以簡要回顧我們的財務狀況以及資產負債表要點。安東尼？

Thanks, Peter. The company reported a net loss of $2.1 million or $0.70 per share for the three months ended September 30, 2024, compared to a net loss of $3.2 million or $6.36 per share for the three months ended September 30, 2023.

謝謝，彼得。該公司報告截至2024年9月30日的三個月淨虧損為210萬美元，即每股0.70美元，而截至2023年9月30日的三個月，淨虧損為320萬美元，即每股6.36美元。

Research and development expense for the three months ended September 30, 2024, decreased to $1.3 million compared to $2.3 million for the three months ended September 30, 2023, primarily due to decreased manufacturing expenses related to drug product releases as well as a decrease in expense related to our clinical trial for BP1001 in AML due to timing of patient enrollment during the quarter.

截至2024年9月30日止三個月的研發費用減少至130萬美元，而截至2023年9月30日止三個月的研發費用為230萬美元，主要是由於與藥品發布相關的製造費用減少以及費用減少由於本季度患者入組時間安排，與我們針對 AML 的 BP1001 臨床試驗相關。

General and administrative expense for the three months ended September 30, 2024, increased to $1.3 million compared to $1.0 million for the three months ended September 30, 2023, primarily due to increased legal fees and salaries and benefits expense. As of September 30, 2024, the company had cash of $0.6 million compared to $1.1 million as of December 31, 2023.

截至2024年9月30日止三個月的一般及行政費用增加至130萬美元，而截至2023年9月30日止三個月則為100萬美元，主要是由於法律費用以及工資和福利費用增加。截至 2024 年 9 月 30 日，該公司擁有現金 60 萬美元，截至 2023 年 12 月 31 日為 110 萬美元。

Net cash used in operating activities for the nine months ended September 30, 2024, was $7.7 million compared to $9.7 million for the comparable period in 2023. Net cash provided by financing activities for the nine months ended September 30, 2024, was $7.2 million.

截至 2024 年 9 月 30 日的九個月，經營活動使用的現金淨額為 770 萬美元，而 2023 年同期為 970 萬美元。截至 2024 年 9 月 30 日的九個月，融資活動提供的淨現金為 720 萬美元。

With that, I'll now turn the call back over to Peter.

這樣，我現在將把電話轉回給彼得。

Thanks, Anthony. As you can see, we continue to make meaningful progress, both advancing and expanding our DNAbilize platform. Our oncology programs continue to enroll, moving us one step closer towards our mission to deliver a better path for cancer patients.

謝謝，安東尼。正如您所看到的，我們繼續取得有意義的進展，推進並擴展我們的 DNAbilize 平台。我們的腫瘤學課程繼續招生，使我們離為癌症患者提供更好的治療途徑的使命又更近了一步。

We are excited by our expansion into the obesity and metabolic space, and look forward to keeping you apprised of our plans as they unfold. Collectively, the progress we are making across our pipeline is setting the stage for a strong finish to the year as we work to bring new medicines to patients in need while creating value for our stakeholders.

我們對肥胖和代謝領域的擴張感到興奮，並期待讓您隨時了解我們的計劃。總的來說，我們在管道上取得的進展為今年的強勁收官奠定了基礎，我們致力於為有需要的患者提供新藥，同時為我們的利害關係人創造價值。

With that, operator, we are ready to open the call for questions.

接線員，我們已經準備好開始提問了。

(Operator Instructions)

（操作員說明）

This concludes our question-and-answer session. I would like to turn the conference back over to Peter Nielsen for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給彼得·尼爾森（Peter Nielsen）發表閉幕詞。

Thank you. Thank you, again, everyone, for joining us and for your continued support of Bio-Path. Have a great day.

謝謝。再次感謝大家加入我們以及對 Bio-Path 的持續支持。祝你有美好的一天。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。