Theriva Biologics Inc (TOVX) 2023 Q4 法說會逐字稿

And greetings, and welcome to the Theriva Biologics full year 2023 investor conference call.

您好，歡迎參加 Theriva Biologics 2023 年全年投資者電話會議。

At this time, all participants are in a listen only mode. As a reminder, this conference is being recorded. I would now like to turn the call over to your host Chris Calabrese with LifeSci Advisors. Thank you. You may begin.

此時，所有參與者都處於僅聆聽模式。提醒一下，本次會議正在錄製中。現在我想將電話轉給 LifeSci Advisors 的主持人 Chris Calabrese。謝謝。你可以開始了。

Thank you, operator, and good morning, everyone. Welcome to the Theriva Biologics full year 2023 investor conference call. Leading the call today will be Steven Shallcross, Chief Executive and Chief Financial Officer of Theriva Biologics; Dr. Medel, Qwest guy of General Director of the RevA biologics, European subsidiary, and Dr. Vince wager, Head of Corporate and Product Development of Spiriva biologics are also on the call and will be available to answer questions during the Q&A session.

謝謝接線員，大家早安。歡迎參加 Theriva Biologics 2023 年全年投資者電話會議。今天的電話會議主持人是 Theriva Biologics 執行長兼財務長 Steven Shallcross；RevA biologics 歐洲子公司總經理 Qwest 的 Medel 博士和 Spiriva biologics 公司和產品開發主管 Vince wager 博士也將參加電話會議，並在問答環節回答問題。

The review Biologics issued a press release this morning, which provided operational highlights and included the financial results for the full year ending December 31, 2023. The press release can be found in the Investors section of the Company's website at w. w. w. dot Areva bio.com, together with the annual report on Form 10-K for full year ended December 31, 2023, which we plan to file today with the Securities and Exchange Commission. In addition to the phone line, this call is being streamed live via webcast, which will be archived on the Company website, w. w. w. dot Areva bio.com for 90 days.

Review Biologics 今天早上發布了一份新聞稿，其中提供了營運亮點，並包括截至 2023 年 12 月 31 日的全年財務表現。您可在公司網站 w. w. w. dot Areva bio.com 的「投資者」部分找到新聞稿，同時還可以找到截至 2023 年 12 月 31 日的全年 10-K 表年度報告，我們計劃於今天向美國證券交易委員會提交該報告。除了電話線外，本次電話會議還將透過網路直播進行現場直播，並將在公司網站 w. w. w. dot Areva bio.com 上存檔 90 天。

During this call, certain forward-looking statements regarding Theriva Biologics and DCM Biosciences, current expectations and projections about future events will be made. Generally, the forward-looking statements can be identified by terminologies such as may, should, expects, anticipates, intends, plans, believes, estimates and similar expressions. These statements are based upon current beliefs, expectations and assumptions and are subject to a number of risks and uncertainties, including those set forth in three-V Biologics' filings with the SEC, many of which are difficult to predict.

在本次電話會議中，將做出有關 Theriva Biologics 和 DCM Biosciences 的某些前瞻性陳述、當前預期以及對未來事件的預測。一般來說，前瞻性陳述可以透過諸如可能、應該、預期、預期、打算、計劃、相信、估計和類似表達等術語來識別。這些聲明是基於當前的信念、預期和假設，並受到許多風險和不確定性的影響，包括 Three-V Biologics 向美國證券交易委員會提交的文件中所述，其中許多風險和不確定性難以預測。

No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. The information on this call is provided only as of the date of this call and to review. Biologics undertakes no obligation to update any forward-looking statements contained on this conference call on account of new information, future events or otherwise, except as required by law.

我們不能保證任何前瞻性陳述，實際結果可能與此類陳述有重大差異。本次電話會議的資訊僅截至本次電話會議日提供，僅供審查。除非法律要求，否則 Biologics 不承擔因新資訊、未來事件或其他原因更新本次電話會議中包含的任何前瞻性聲明的義務。

With that, I'd like to turn the call over to Steve.

說完這些，我想把電話轉給史蒂夫。

Thank you, Chris, and good morning. I appreciate everyone for taking the time to join us today. In 2023, we continued to make steady progress to drive forward our oncology forward focused portfolio designed to address unmet needs for difficult to treat cancers. Our primary efforts and resources are focused on pursuing multiple therapeutic opportunities for our lead clinical candidate, VCN-01.

謝謝你，克里斯，早安。我感謝大家今天抽出時間來參加我們的活動。2023年，我們持續穩定地推動以腫瘤學為重點的前瞻性產品組合，旨在解決難治性癌症的未滿足需求。我們的主要努力和資源集中在為我們的主要臨床候選藥物 VCN-01 尋求多種治療機會。

As a reminder, VCN-01 is a systemically administered oncolytic adeno virus designed to selectively replicate within the tumor, the grade the tumor matrix increase tumor immunogenicity. We believe these multiple modes of action position, VCN-01 for optimized tumor killing in combination with chemotherapy and immuno-oncology products and otherwise refractory solid tumors.

提醒一下，VCN-01 是一種全身給藥的溶瘤腺病毒，旨在選擇性地在腫瘤內複製，腫瘤基質的等級增加腫瘤的免疫原性。我們相信，這些多種作用模式使得VCN-01能夠與化療和免疫腫瘤產品結合，優化腫瘤殺傷效果，並治療難治性實體腫瘤。

We have shown that repeated systemic dosing of VCN-01 is feasible from a safety perspective, and we can now focus on whether the repeated dose VCN, Reg VCN-01 regimen may lead to improved clinical outcomes for patients beyond VCN-01, we are pursuing new oncolytic virus candidates to leverage our novel human shield technology, which is designed to protect systemically administered oncolytic viruses from the host immune system and may facilitate more frequent repeated administration of oncolytic virus therapies. This movement may enable our pipeline of products to be used in standardized treatment cycles that are well established in cancer, chemotherapy and immunotherapy.

我們已經證明，從安全角度來看，VCN-01 的重複全身給藥是可行的，現在我們可以專注於重複劑量 VCN、Reg VCN-01 方案是否可以為 VCN-01 以外的患者帶來更好的臨床結果，我們正在尋求新的溶瘤病毒候選藥物，以利用我們新穎的人體治療盾牌這項措施可能使我們的產品系列能夠用於癌症、化療和免疫療法中已成熟的標準化治療週期。

Additionally, as part of our oncology focus portfolio. We continue to screen and enroll patients in the second cohort of the Phase Ib IIa clinical trial of sin for design to prevent potentially fatal adverse outcomes in patients who undergo alginate committed periodic cell transplant ACT. to treat hematologic cancers. With our cash runway into the first quarter of 2025, we believe we're well positioned to execute on our corporate objectives and remain on track to achieving multiple value-enhancing milestones.

此外，作為我們腫瘤學重點產品組合的一部分。我們繼續篩選並招募 Ib IIa 期臨床試驗第二組患者，旨在預防接受藻酸鹽定向定期細胞移植 (ACT) 治療血液系統癌症的患者出現潛在的致命不良後果。隨著我們的現金流進入 2025 年第一季度，我們相信我們已準備好實現我們的企業目標，並繼續實現多個增值里程碑。

With this brief introduction, I'd like to expand on key pipeline updates. Starting with our lead program. VCN-01 BCL. one has been administered to more than 100 patients across diverse indications, which speaks to the broad therapeutic potential, including pancreatic ductal adenocarcinoma or PDX retinol BLISS, stoma, head and neck squamous cell carcinoma, colorectal cancer and ovarian cancer.

透過這個簡短的介紹，我想詳細介紹一下關鍵的管道更新。從我們的主導計劃開始。VCN-01 BCL.one 已用於治療 100 多名不同適應症的患者，這表明其具有廣泛的治療潛力，包括胰腺導管腺癌或 PDX 視黃醇 BLISS、造口、頭頸部鱗狀細胞癌、結直腸癌和卵巢癌。

VCN-01 has been granted orphan drug designation in the US and Europe for the treatment of pancreatic cancer and in the US for retinol, but Soma, providing additional opportunities for regulatory engagement and if approved market exclusivity, our most advanced program for VCN-01 is in PDX for which incidence continues to rise in an indication that has one of the lowest survival rates among all cancers.

VCN-01 已在美國和歐洲被授予治療胰腺癌的孤兒藥稱號，在美國被授予治療視黃醇的孤兒藥稱號，但 Soma 為監管參與提供了額外的機會，如果獲得市場獨佔權批准，我們最先進的 VCN-01 項目是在 PDX 中，該疾病的發病率持續上升，而該疾病是所有癌症中存活率最低的疾病之一。

It is well established that the pediatric tumor matrix is one of the key reasons for the overall poor therapeutic outcomes for these patients. We believe the CNO one's differentiated mechanism of action has the potential to address the urgent need for new treatment options for patients with PTAC. by degrading the twofer matrix and increasing tumor access by co administering cancer therapies. We are pleased to report that dosing is well underway for Viraj, our Phase 2b trial of VCN-01 in combination with standard of care chemotherapy, gemcitabine and nab-paclitaxel, which is being evaluated as a first-line therapy for patients with PDX with six sites open in the US and nine sites opened in Spain. Faraj remains on track to complete enrollment in the first half of 2024.

眾所周知，兒童腫瘤基質是這些患者整體治療效果不佳的主要原因之一。我們相信，CNO one 的差異化作用機制有可能解決 PTAC 患者對新治療方案的迫切需求。透過降解二聚體基質並透過共同施用癌症療法來增加腫瘤的可及性。我們很高興地報告，Viraj 的給藥進展順利，這是我們的 2b 期試驗，將 VCN-01 與標準化療、吉西他濱和白蛋白結合型紫杉醇相結合，正在評估其作為 PDX 患者的一線治療方案，目前在美國有 6 個中心開放，在西班牙有 9 個中心開放。Faraj 預計將在 2024 年上半年完成入學。

In the first quarter of 2024, we completed the first safety review with the Independent Data Monitoring Committee or IDMC with a positive recommendation from the IDMC. Faraj will continue to enroll patients without any changes to the protocol. Notably, intravenous VCN-01 has been well tolerated and demonstrated a safety profile consistent with prior clinical trials.

2024 年第一季度，我們與獨立資料監測委員會 (IDMC) 完成了第一次安全審查，並獲得了 IDMC 的積極建議。Faraj 將繼續招募患者，且不會對治療方案進行任何改變。值得注意的是，靜脈注射 VCN-01 耐受性良好，並表現出與先前的臨床試驗一致的安全性。

Importantly, no additional toxicities were observed in patients receiving a second dose of VCN-01, providing the first clinical evidence of the feasibility of repeated systemic dosing. As a reminder, primary endpoints for the Virage trial include overall survival and BCNO. one safety and tolerability. Additional endpoints include progression-free survival objective response rate measures of VCN-01 biodistribution replication, immune response and measures of the quality of life of treated patients. Since this is an open-label trial, progress will be monitored very closely in steps to accelerate the clinical program may be implemented if supported by emerging data.

重要的是，接受第二劑 VCN-01 的患者沒有觀察到額外的毒性，這為重複全身給藥的可行性提供了第一個臨床證據。提醒一下，Virage 試驗的主要終點包括總體存活率和 BCNO。安全性和耐受性。其他終點包括 VCN-01 生物分佈複製的無惡化存活期客觀反應率測量、免疫反應和接受治療的患者的生活品質測量。由於這是一項開放標籤試驗，因此將逐步密切監測進展情況，以便在有新數據支持的情況下加速實施臨床計劃。

More broadly, the Virage trial will enable us to determine the feasibility of repeated dosing of VCN-01 This could shift the approach to standardize treatment cycles that are well established in cancer chemotherapy and immunotherapy and may lead to improved clinical outcomes for patients with PDX and other difficult to treat solid tumors.

更廣泛地說，Virage 試驗將使我們能夠確定 VCN-01 重複給藥的可行性，這可能會改變癌症化療和免疫治療中已建立的標準​​化治療週期的方法，並可能改善 PDX 和其他難以治療的實體瘤患者的臨床結果。

In addition to advancing the Virage PDN trial, we continue to work closely with key opinion leaders in the US, Europe and Central and South America, as well as with regulatory agencies to refine our clinical strategy in Renovo stoma. We believe intravitreal VCN-01 has the potential to treat vitreous seeds in children with retinol Bluestone.

除了推進 Virage PDN 試驗外，我們還繼續與美國、歐洲、中美洲和南美洲的關鍵意見領袖以及監管機構密切合作，以完善我們在 Renovo 造口方面的臨床策略。我們相信玻璃體內注射 VCN-01 有潛力治療患有視黃醇藍石的兒童玻璃體種子。

Since current clinical practice varies in, there's no regulatory guidance specific to retinol plus stoma drug development. We held a pre IND meeting with the FDA in the fourth quarter of 2023 to discuss the development pathway for VCN-01 is an adjunct to chemotherapy in pediatric patients with advanced renal milestones. During our meeting with the FDA, we were provided some guidance on the potential endpoints in patient population for an advanced clinical trial and encouraged to submit a formal protocol under a US IND.

由於目前的臨床實踐各不相同，因此沒有針對視黃醇加造口藥物開發的監管指導。我們於 2023 年第四季與 FDA 舉行了 IND 前會議，討論 VCN-01 作為晚期腎臟里程碑兒童化療輔助手段的開發途徑。在與 FDA 會面期間，我們獲得了有關高級臨床試驗患者群體潛在終點的一些指導，並被鼓勵根據美國 IND 提交正式方案。

In order to provide a more detailed commentary for this program, we are encouraged by interactions with the FDA and look forward to driving this program forward.

為了對該計劃提供更詳細的評論，我們與 FDA 的互動令人鼓舞，並期待推動該計劃向前發展。

In parallel with company-sponsored studies, the potential utility of VCN-01 is being explored and a number of investigator-sponsored studies that are underway at leading oncology research institutions around the world, notably collaborators at St. Johns and Dale have completed patient treatment in the Phase one investigator sponsored trial evaluating the safety and activity of intravitreal BC and one in pediatric patients with refractory retinol Bluestone.

在公司贊助的研究開展的同時，VCN-01 的潛在效用也正在被探索，並且全球領先的腫瘤學研究機構正在進行多項由研究者贊助的研究，特別是聖約翰斯和戴爾的合作者已經完成了第一階段研究者贊助的試驗中的患者治療，該試驗評估了玻璃體內注射 BC 的安全性和活性，以及​​一項針對兒科難治性的黃醇試驗針對兒科的難治性。

The trial evaluated escalating doses of VCN-01 administered by two intravitreal injections separated by 14 days and remains on track to complete patient follow-up in the first half of 2024, which will help to inform the planned Phase 2 trial and design and the protocol. As a reminder, preclinical data has shown that topotecan treatment enhanced BCNO. one oncolytic activity against rentable stoma and more broadly reinforced VCN-01 possibility as an adjunct to intravitreal chemotherapy in patients who fail currently available treatments. We remain encouraged by the potential of this novel combination approach to provide superior clinical benefits for children with this devastating cancer.

該試驗評估了間隔 14 天的兩次玻璃體內注射所給予的 VCN-01 的遞增劑量，並預計在 2024 年上半年完成患者隨訪，這將有助於為計劃中的第 2 階段試驗和設計以及方案提供資訊。提醒一下，臨床前數據表明，拓撲替康治療增強了 BCNO。一種針對可出租造口的溶瘤活性，並且更廣泛地加強了 VCN-01 作為目前可用治療失敗的患者玻璃體內化療輔助手段的可能性。我們仍然對這種新型組合療法的潛力感到鼓舞，它能為患有這種毀滅性癌症的兒童提供卓越的臨床益處。

Additionally, the University of Pennsylvania continues to enroll and treat patients in their Phase one investigator sponsored trial, administering VCN-01 with your CAR T muscle cells to patients with ovarian or pancreatic cancers. VCN-01 designed to increase tumor immunogenicity and improve access by additional therapies such as UCargo muscle cells while cell-based immunotherapies have had limited efficacy against solid tumors to date, we are encouraged by initial results highlighting the feasibility of administering VCN-01 with this type of CAR T therapy. These preliminary results were presented last year at the Society for Immunotherapy of Cancer Annual Meeting or cities. European investigators are continuing to explore the optimal dosing regimen for VCN-01 co-administered with your card muscle cells, and we look forward to further data from the study in 2024.

此外，賓州大學繼續招募和治療其第一階段研究者贊助的試驗中的患者，向卵巢癌或胰腺癌患者施用帶有 CAR T 肌肉細胞的 VCN-01。VCN-01 旨在提高腫瘤免疫原性並改善透過 UCargo 肌肉細胞等其他療法獲得的治療，而迄今為止基於細胞的免疫療法對實體瘤的療效有限，我們對初步結果感到鼓舞，強調了使用這種類型的 CAR T 療法管理 VCN-01 的可行性。這些初步結果於去年在癌症免疫治療學會年會上發表。歐洲研究人員正在繼續探索VCN-01與你的卡肌細胞共同給藥的最佳給藥方案，我們期待2024年獲得該研究的進一步數據。

Turning to our ongoing Phase 2b 2a clinical trial of Washington University evaluating same for or write-backs. The trials designed to evaluate the therapeutic potential of sin for two fatal to reduce fatal adverse events related to IV beta-lactam antibiotic use and allogeneic HCT recipients, including acute graft versus host disease or AGVHD. in overgrowth and infection by pathological organisms such as C. difficile and Vanco myosin resistant and tear Koksay. The Phase 1b 2a study is designed to assess the feasibility of using sense for and consist of three sequential cohorts comparing different IV beta-lactam antibiotics following conditioning therapy in each cohort eight patients will receive and four and four receive placebo. While the data remain blinded, interim analysis suggests it's in four is well tolerated and was not observed in the blood samples of a majority of development patients.

談到我們正在進行的華盛頓大學 2b 2a 期臨床試驗，評估相同的或回寫的情況。該試驗旨在評估sin對兩種致命藥物的治療潛力，以減少與靜脈注射β-內酰胺類抗生素使用和異基因造血幹細胞移植接受者相關的致命不良事件，包括急性移植物抗宿主疾病（AGVHD）。在過度生長和感染病理生物體（如艱難梭菌和Vanco肌球蛋白抗藥性和撕裂Koksay）方面。1b 2a 期研究旨在評估使用 sense 的可行性，由三個連續隊列組成，比較不同 IV β-內酰胺類抗生素的預處理療法，每個隊列中有 8 名患者接受治療，另有 4 名患者接受安慰劑治療。雖然數據仍然是盲測的，但中期分析表明，四種藥物耐受性良好，並且在大多數開發患者的血液樣本中未觀察到。

Our second cohort is underway and is designed to evaluate SIN for combination with piperacillin tazobactam. The trial is on track to complete enrollment in the second cohort in the second quarter of 2024. This cohort will provide important additional safety information. In particular, whether oral sema four has the potential to alter IV antibiotic levels in this patient population. We look forward to sharing this data in the second half of 2024.

我們的第二批研究正在進行中，旨在評估 SIN 與哌拉西林他唑巴坦的合併用藥。該試驗預計於 2024 年第二季完成第二批患者的招募。該群體將提供重要的額外安全資訊。特別是口服 sema four 是否有可能改變該患者群體的靜脈抗生素水平。我們期待在 2024 年下半年分享這些數據。

Overall, we are encouraged by the progress across our pipeline in the growing clinical data that underscore the promise of our systemically administered oncolytic virus in key indications and combinations. We remain focused on driving our clinical programs forward in exploring opportunities to leverage our novel albumin shield technology and exciting additional technologies from Rovi discovery platform. I'm confident that the Company's upcoming catalysts will provide a solid foundation for execution and value creation.

總體而言，我們對不斷增長的臨床數據中整個管道的進展感到鼓舞，這些數據強調了我們系統性給藥的溶瘤病毒在關鍵適應症和組合中的前景。我們將繼續致力於推動臨床項目向前發展，探索利用我們新穎的白蛋白屏蔽技術和 Rovi 發現平台令人興奮的附加技術的機會。我相信公司即將出現的催化劑將為執行和價值創造奠定堅實的基礎。

Specifically we remain on track to complete enrollment for the Virage study in the first half of 2024, complete follow-up in the Phase 1 investigator sponsored trial evaluating the safety and activity of intravitreal, the VCN-01 in pediatric patients with refractory reasonable stoma and the first half of 2024 and complete enrollment in the second cohort of our Phase 1b 2a clinical study of seven four for the prevention of AGVHD. in bone marrow transplant patients in the second quarter of 2024.

具體來說，我們仍有望在 2024 年上半年完成 Virage 研究的招募，在 2024 年上半年完成由研究者發起的評估玻璃體內註射 VCN-01 對難治性造口兒科患者的安全性和活性的 1 期研究者試驗的隨訪，並在 2024 年第二季度完成 1b/2a 期進行 1b/2a 期研究者的研究者招募了該骨髓 AGV 對骨髓 的 1b/2a 期。

Now I briefly turn to our financial results for the first full year ended at December 31, 2023, general and administrative expenses decreased to $7.1 million for the year ended December 31, 2023 from $9.9 million for the year ended December 31, 2022. This decrease of 28% is primarily comprised of the decrease in the fair value of the contingent consideration of $2.8 million, along with lower salary, investor relations, legal costs, consulting fees related to the VCN. acquisition and director and officer insurance, offset by higher audit fees and other consulting fees.

現在我簡要介紹截至 2023 年 12 月 31 日的第一個全年財務業績，一般和行政費用從截至 2022 年 12 月 31 日的 990 萬美元減少到截至 2023 年 12 月 31 日的 710 萬美元。這一 28% 的下降主要由於或有對價的公允價值下降 280 萬美元，以及與 VCN 收購和董事及高管保險相關的薪酬、投資者關係、法律成本、諮詢費降低，但被更高的審計費和其他諮詢費所抵消。

The charge related to stock-based compensation expense was $0.4 million for the year ended December 31, 2023 compared to $0.4 million for the year ended December 31, 2022. Research and development expenses increased to $14.3 million for the year ended December 31, 2023 from $11.7 million for the year ended December 31, 2022.

截至 2023 年 12 月 31 日止年度，與股票薪酬費用相關的費用為 40 萬美元，截至 2022 年 12 月 31 日止年度為 40 萬美元。研發費用從截至 2022 年 12 月 31 日止年度的 1,170 萬美元增加至截至 2023 年 12 月 31 日止年度的 1,430 萬美元。

This increase of 22% is primarily the result of higher clinical trial expenses related to our Virage Phase 2 clinical trial of VCN-01 and PDx offset by lower expenses related to our Phase 1b 2a clinical trial of sin for an allogeneic HCT recipients. The completed phase one, a clinical trial have seen 20 decreased manufacturing expenses related to our Phase 1a clinical trials in 20 and lower other indirect costs.

這一 22% 的增長主要是由於與我們的 Virage VCN-01 和 PDx 第 2 階段臨床試驗相關的臨床試驗費用增加，但與針對異基因 HCT 接受者的 sin 第 1b 2a 階段臨床試驗相關的費用降低相抵觸。完成的第一階段臨床試驗使我們 20 年 1a 期臨床試驗相關的製造費用減少了 20%，其他間接成本也降低了。

We anticipate research and development expense to increase as we continue enrollment in our Virage Phase two clinical trial of VCN-01 and P. deck in our ongoing Phase 1 clinical trial and renewable stoma, expand GMP manufacturing activities for VCN-01 and continue supporting RBC and 11 on other preclinical and discovery initiatives.

我們預計研發費用將會增加，因為我們將繼續招募 VCN-01 的 Virage 第二階段臨床試驗和正在進行的第一階段臨床試驗和可再生造口的 P. deck，擴大 VCN-01 的 GMP 製造活動，並繼續支持 RBC 和 11 進行其他臨床前和發現計劃。

Research and development expense also includes a charge related to noncash stock-based compensation expense of $165,000 for the year ended December 31, 2023, compared to $112,000 for the year ended December 31, 2022. Other income was $1,442,000 for the year ended December 31st, 2023, compared to other income of $471,000 for the year ended December 31, 2022. Other income for the year ended December 31, 2024, was primarily comprised of interest income of $1,439,000 and an exchange gain of $3,000. Other income for the year ended December 31, 2022 is primarily comprised of interest income of $512,000, offset by an exchange loss of $41,000.

研發費用還包括截至 2023 年 12 月 31 日止年度的非現金股票薪酬費用 165,000 美元，截至 2022 年 12 月 31 日止年度為 112,000 美元。截至 2023 年 12 月 31 日止年度的其他收入為 1,442,000 美元，而截至 2022 年 12 月 31 日止年度的其他收入為 471,000 美元。截至 2024 年 12 月 31 日止年度的其他收入主要包括利息收入 1,439,000 美元和匯兌收益 3,000 美元。截至 2022 年 12 月 31 日止年度的其他收入主要包括 512,000 美元的利息收入，但被 41,000 美元的匯兌損失所抵銷。

Cash and cash equivalents totaled $23.2 million as of December 31, 2023, compared to $41.8 million as of December 31, 2022. We remain deeply committed to improving patient outcomes for these very hard-to-treat cancers.

截至 2023 年 12 月 31 日，現金及現金等價物總額為 2,320 萬美元，而截至 2022 年 12 月 31 日為 4,180 萬美元。我們始終堅定地致力於改善這些極難治療的癌症患者的治療效果。

And before we conclude today's call, I want to extend my sincere appreciation and gratitude for the foundational work that has brought us closer to delivering on our mission.

在我們結束今天的電話會議之前，我想對那些讓我們更接近完成使命的基礎工作表示誠摯的感謝和感激。

I'd like to thank the entire Theriva team, our investors and the many people who have been supportive along the way, including our patients and their families.

我要感謝整個 Theriva 團隊、我們的投資者以及一路以來給予我們支持的許多人，包括我們的患者及其家人。

With that, we're happy to take questions.

我們很樂意回答您的問題。

Thank you. And at this time, we'll be conducting a question and answer session. (Operator Instructions)

謝謝。此時，我們將進行問答環節。（操作員指示）

James Molloy, Alliance Global Partners.

聯盟全球合作夥伴的詹姆斯‧莫洛伊 (James Molloy)。

Yes, good morning. Thank you very much for taking my questions. Pillow had a question looking below Stephen, Alex, Christopher, just even your mental on looking across the multiple IST.s, which are very cost efficient way of getting trials done excellent. Excellent use of capital, which you guys see as sort of most promising of like all the volatile and of course, of which seems like it might be maybe growing the task. We look across the thrust of the plethora of IST as you guys have got underway.

是的，早安。非常感謝您回答我的問題。Pillow 有一個問題，請看 Stephen、Alex、Christopher 的回答，即使你們只是在思考多個 IST，這也是非常經濟有效的出色完成試驗的方法。資本的出色利用，你們認為這是所有波動性中最有希望的，當然，這似乎可能會增加任務。隨著你們的前進，我們開始關注 IST 的大量進展。

So let me let me just highlight where what we've got going on once again. And then Manav, you could talk specifically about some of the exciting findings that we found of had disclosed at various scientific conferences. So as you're aware, we put out some incredible head and neck cancer data at asthma last October. This is using BC and one in combination with checkpoint inhibitors in patients that were refractory to previous rounds of checkpoint inhibitor therapy on someone else could talk a little bit about that.

因此，讓我再次強調我們正在做的事情。然後，馬納夫，您可以具體談談我們在各個科學會議上發現的一些令人興奮的發現。如你所知，我們去年 10 月發布了一些關於氣喘的令人難以置信的頭頸癌數據。這是將 BC 與檢查點抑制劑聯合用於對之前幾輪檢查點抑制劑療法有抵抗力的患者，其他人可以稍微談談這一點。

We've got the retinol Bluestone, the program on which we've just concluded, and now we're in the middle of follow-up. And then we've got the ongoing New Penn study, which is down to of their organization, trying to isolate the right dose take forward. So we would expect to see some more of data sometime this year related to the work they're doing there.

我們已經獲得了視黃醇 Bluestone，該項目剛剛結束，現在我們正在進行後續跟進。然後，我們進行了正在進行的新賓州研究，該研究由他們的組織負責，試圖找出正確的劑量。因此，我們希望今年某個時候能看到更多與他們在那裡所做的工作相關的數據。

So now maybe you could just highlight the important findings on those three studies that are that are ongoing or recently completed?

那麼現在您能否強調一下正在進行或最近完成的這三項研究的重要發現？

Yes, sure, sure. So obviously, the muscle complete data, let's say, from the trial in head and neck had a good percentage of asthma in October as you know, this was a trial combining VISION one with the development and efficient refractory to the action of immune checkpoint inhibitors in head and neck carcinoma.

是的，當然，當然。因此，顯然，從頭頸部試驗中獲得的完整肌肉數據顯示，十月份氣喘的比例很高，這是一項將 VISION 1 與頭頸部癌中免疫檢查點抑制劑的作用的開發和有效抗藥性相結合的試驗。

Okay. And we have previously presented safety data that demonstrated that additional one has an acceptable safety profile when administered prior to durvalumab. And in this new presentation that we conducted in October, we presented data on efficacy.

好的。我們之前已經提供了安全數據，證明在使用 durvalumab 之前使用另一種藥物具有可接受的安全性。在我們十月進行的這次新演示中，我們展示了功效的數據。

And we have seen that the patients treated with Vision Show with an increase of restaurants, two, a subset of chemotherapy treatments after progressions and style. But specifically, we have also seen that the survival of patients has been large for a number of patients. And in fact, some patients are still alive more than four years after we didn't participate in the trial, which in my view, it's quite remarkable because those patients were entering the trial had some effect on shelf life of between three or four months. And what we are seeing obviously, it's really interesting.

我們已經看到，接受 Vision Show 治療的患者在餐廳數量、兩種化療治療的進展和風格方面都有所增加。但具體來說，我們也看到，對許多患者來說，患者的存活率很高。事實上，有些患者在我們沒有參加試驗後仍然存活了四年多，在我看來，這是非常了不起的，因為這些患者參加試驗對三到四個月的保質期有一定影響。顯然，我們看到的現象確實很有趣。

And moreover, it's not just a question of efficacy that does a very good correlation between the restaurants and the biological data we are getting from the tumor biopsies of these patients. And in fact, we have seen down-regulation of the more massive genes. We have been observing increasing levels of immune markers in the tumor biopsies. And interestingly, there was a correlation between the survival and with the CPS score and a day after vision one for investigator scoring, it's a kind of marker about immunological status and what looks in our biological, the that you said that vision one treatment change in this environment and definite correlation between the magnitude of the change that we use and the survival of patients, which is I think exciting.

此外，這不僅僅是療效的問題，餐廳與我們從這些患者的腫瘤活檢中獲得的生物數據之間存在很好的相關性。事實上，我們已經看到了更大基因的下調。我們一直在觀察腫瘤活檢中免疫標記的水平不斷增加。有趣的是，生存率與 CPS 評分之間存在相關性，並且與視覺一後一天的研究者評分存在相關性，它是關於免疫狀態​​和我們生物學狀況的一種標記，您說視覺一治療在這種環境下發生了變化，並且我們使用的變化幅度與患者的生存率之間存在明確的相關性，我認為這令人興奮。

Obviously, it's use a proportion, but it's exciting in regional customer. We have been treating more patients. We have seen some patients with reductions that we do see it. But specifically, we have been also collecting data of combination with the chemotherapy, the chemotherapy that is using rational estimate, it's topotecan. And in this trial, we have seen not derailing the clinical patients. But in preclinical work that we have done with biopsies and from a human cells, we have been observing that there is synergy between the action of this in one and a couple of Beacon, which is very encouraging and opens the door for a combination approach in our Phase two program that is massively with cash and with FDA in our meeting.

顯然，它只佔一定比例，但在區域客戶中卻令人興奮。我們一直在治療更多的病人。我們已經看到一些患者的病情有所減輕。但具體來說，我們也一直在收集與化療合併使用的數據，使用合理估計的化療是拓樸替康。而在這次試驗中，我們看到了沒有脫軌的臨床患者。但在我們對活檢和人體細胞進行的臨床前工作中，我們觀察到 Beacon 的單一作用和多個作用之間存在協同作用，這非常令人鼓舞，並為我們在第二階段計劃中採用組合方法打開了大門，該計劃大量使用了現金，並在我們與 FDA 的會議上投入了大量資金。

Okay.

好的。

So basically, the data we are collecting, it's very exciting. And in my view, it's very exciting to see that in different indications, we can confirm the mechanism of action. And we can see initial evidence of activity in happening in RightNow customer, which is also the same thing that we have observed in our Phase one program in pancreatic cancer so that the data is quite consistently that way.

所以基本上，我們收集的數據非常令人興奮。在我看來，看到我們能夠在不同的適應症中確認作用機制是非常令人興奮的。我們可以看到 RightNow 客戶中正在發生的活動的初步證據，這也是我們在第一階段胰腺癌計畫中觀察到的相同情況，因此數據是相當一致的。

Thank you very much. Taking my quick follow-up on the on the retina. Last on the ISTI. when you anticipate potentially filing an IND and starting the Phase two three again, presuming the Phase one wraps up as you hope.

非常感謝。對視網膜進行快速跟進。最後是 ISTI。當您預計可能提交 IND 並再次開始第二階段時，假設第一階段如您所願結束。

And then a follow-up to the Phase IIb Virage, I know the enrollment completed in first half 2024, which we just data final data top line data for us.

然後是第二階段 Virage 的後續工作，我知道招生工作將於 2024 年上半年完成，我們剛剛收集了最終數據頂線數據。

So Manoj, why don't you take the first one and then Vince, you could take the second guess our four original restaurant model right now we are just following the a lot of patients.

那麼 Manoj，你為什麼不選擇第一個，然後 Vince，你可以選擇第二個，猜測一下我們最初的四個餐廳模式，現在我們只是在關注很多病人。

Okay. As you know, our clinical trial to treat the patient that part, it's already finished that we need to follow the patients for six months after the last dosing. So we are expecting to finish our database with data of the trial in mid-2024, probably. And after that, we need to rise to interest a rep or and start that discussion with FDA. The final design of the and the so I don't expect to go for an IND until 2024, 2025, sorry by shore because obviously we need to finish some activities. We got before submitting any AMD for RightNow customer base. We want to give some color on the pancreatic program.

好的。如您所知，我們治療該部分患者的臨床試驗已經完成，我們需要在最後一次服藥後對患者進行六個月的追蹤。因此，我們預計大概在 2024 年中期完成包含試驗資料的資料庫。之後，我們需要引起代表的興趣或與 FDA 展開討論。最終的設計，所以我預計要到 2024 年、2025 年才會進行 IND，很抱歉，因為我們顯然需要完成一些活動。在為 RightNow 客戶群提交任何 AMD 之前，我們就已獲得這些資訊。我們想對胰臟計劃做一些說明。

Thanks, Menno. So I'll as Steve indicated, a Virage study is enrolling and we anticipate completing enrollment in the first half of this year with the with the patients only. And then we will be very closely monitoring the emergence of our data. And this there's two key outcomes one. Obviously, our primary endpoint of survival will be following those patients and the longer the better from our perspective because we want to have a good effect.

謝謝，門諾。因此，正如史蒂夫所指出的，Virage 研究正在招募新成員，我們預計將在今年上半年完成招募，僅限患者。然後我們將密切監控我們數據的出現。這有兩個關鍵成果。顯然，我們的主要生存終點將是追蹤這些患者，從我們的角度來看，時間越長越好，因為我們希望取得良好的效果。

So the primary endpoint data. The survival won't read out until next year as I kind of peak when we would like to say that to be potentially in the second half, the longer as long as these patients keep going. We want patients on our drug to do well.

因此為主要終點數據。存活率要到明年才能公佈，我想說，存活率可能會在下半年達到高峰，只要這些病人繼續存活，存活時間就會更長。我們希望服用我們藥物的患者能夠康復。

In the interim, we will be looking at our data to see if there's something that we can around which we can build a formal interim analysis to review with the FDA and discuss next steps how we can potentially advance our program quickly into a pivotal trial. And as we know, as you know, we've got the orphan drug designation, so we'll leverage that strategy. But again, we can't necessarily predict the timing other than later in the year for a potential interim analysis if we choose to do one. But the overall endpoints for the primary endpoint of survival will be next year

在此期間，我們將查看我們的數據，看看是否可以建立正式的中期分析，以便與 FDA 一起審查，並討論下一步如何快速推進我們的計畫進入關鍵試驗階段。正如我們所知，正如您所知，我們已獲得孤兒藥稱號，因此我們將利用該策略。但是，如果我們選擇進行中期分析的話，我們無法預測除了今年稍後之外的時間。但生存的主要終點的總體終點將是明年

Thank you very much. And maybe a follow-up questions from me on Cyno forking giving you actually sort of the endgame for CNO for where a so what though which we anticipate sort of coming to a conclusion on that on the data, what sort of timing on that? And then can you talk a little bit about how the partnership and characterize the partnership environment currently for Finjan licensing OTOR. for linear compounds?

非常感謝。也許我接下來會問一個關於 Cyno 分叉的問題，實際上可以告訴你 CNO 的最終結果，那麼我們預計會根據數據得出結論，時間是什麼時候？然後，您能否稍微談談合作夥伴關係以及目前 Finjan 授權 OTOR 線性化合物的合作環境？

Sure. So on, as you know, the same for trials, a single single-site study at Wash U and those partners have been outstanding on fortunately or unfortunately, on the time it takes to enroll a trial like that is subject to the number of patients that actually meet the screening criteria so they can be brought into the trial and we're going to complete that trial, as I stated earlier on in relative short order.

當然。因此，如您所知，試驗也是一樣，華盛頓大學的單一地點研究和那些合作夥伴一直表現出色，幸運的是或不幸的是，參加此類試驗所需的時間取決於實際符合篩選標準的患者人數，因此他們可以參與試驗，我們將在相對較短的時間內完成該試驗，正如我之前所說的那樣。

And then we'll obviously have some disclosure around that. This cohort is pretty important because a sin for does degrade the combination of pepper so on and take it back to him. And obviously, we're monitoring the data in this trial and we want to make sure that the antibiotic is not and interfered with in this more fragile patient population.

然後我們顯然會對此進行一些披露。這個群體非常重要，因為罪惡確實會降低胡椒的組合，並將其帶回給他。顯然，我們正在監測這次試驗的數據，我們希望確保抗生素不會對這個更脆弱的患者族群造成乾擾。

So once we have that data in hand, we'll make a decision about whether or not we advance into the third cohort or whether or not we have enough and to answer our questions that were brought to us by the FDA on then this asset ties in more broadly to the initiatives we have underway to identify potential partners across our entire pipeline. So we've hired some outside advisors on one group specific to help us finding a home for person for and we've had engagement.

因此，一旦我們掌握了這些數據，我們就會決定是否進入第三批，或者是否有足夠的數據，並回答 FDA 向我們提出的問題，然後這項資產將更廣泛地與我們正在進行的計劃聯繫在一起，以確定我們整個管道中的潛在合作夥伴。因此，我們聘請了一些外部顧問來專門幫助我們為員工找到歸宿，並且我們已經與他們進行了接觸。

And again, a lot of this has to do about when we have the data on. We've also have a group we're working with and outreach to potential partners for the VCNO. one platform. And once again, we've had multiple engagements and interest and we will continue those discussions. And once again, data is key and we've also have some folks that we're working with trying to find a home for the Cine 20 program.

再次強調，這很大程度取決於我們何時獲得數據。我們還有一個正在合作的團隊，正在為 VCNO.one 平台聯繫潛在的合作夥伴。再次強調，我們已經進行了多次接觸並獲得了廣泛關注，我們將繼續進行這些討論。再次強調，數據是關鍵，我們也正在與一些人合作，嘗試為 Cine 20 程式找到一個歸宿。

And again, those discussions are ongoing. I think the environment has gotten a bit better recently on, I think over the last couple of years, given sort of the bear market that biotech and small and micro-cap biotech has been and has hindered a lot of discussion on, but I am more and more optimistic things seem to be picking up a little bit. And in keeping with our strategy and how we view these ongoing discussions we're not going to talk about specific interactions and when we have something, obviously we'll make a disclosure about that, of course.

再次強調，這些討論仍在進行中。我認為最近環境已經好轉了一些，我認為在過去幾年裡，考慮到生物技術和小型和微型生物技術的熊市阻礙了很多討論，但我越來越樂觀地認為事情似乎正在好轉。為了符合我們的策略以及我們對這些正在進行的討論的看法，我們不會談論具體的互動，當然，當我們有消息時，我們當然會披露。

Thank you very much taking questions.

非常感謝您回答問題。

Thank you. And as a reminder, if you'd like to ask a question, please press star one on your telephone keypad or pause a moment to allow for any other question. Mr. Shah cross.

謝謝。提醒一下，如果您想提問，請按電話鍵盤上的星號或暫停片刻以回答其他問題。沙阿先生交叉。

I'm not showing any other questions at this time. I'll turn the floor back to you for any final.

我目前沒有顯示任何其他問題。我將把最終發言權交還給你。

Okay. Thanks, Melissa. Well, thanks again, everyone, for taking the time to join us today. I hope you sense that we're incredibly focused on driving all of our programs forward.

好的。謝謝，梅麗莎。好吧，再次感謝大家今天抽出時間來參加我們的活動。我希望您能感受到我們非常專注於推動所有專案向前發展。

We're doing this in a way which I think we're very good stewards with our cash and making and stretching that dollar the best we can to get as much data and as many clinical outcomes and results as possible.

我認為，我們這樣做是因為我們非常善於管理我們的資金，並盡可能地充分利用這些資金來獲取盡可能多的數據和盡可能多的臨床結果。

Will continue is we just ended with Jim here to evaluate our strategic options, and we'll continue to look for ways to drive additional value for our shareholders and for the long-term success of what we're trying to do namely delivering, you know, promising treatments for very, very difficult-to-treat cancers.

我們將繼續與吉姆一起評估我們的策略選擇，我們將繼續尋找方法為股東創造額外價值，並為我們正在努力做的事情的長期成功提供保障，即為非常非常難以治療的癌症提供有希望的治療方法。

Thanks again for joining us, and we look forward to keeping you updated on our progress.

再次感謝您的加入我們，我們期待向您通報我們的進展。

Thank you. This concludes today's conference. You may disconnect your lines at this. Thank you for your participation.

謝謝。今天的會議到此結束。此時您可以斷開線路。感謝您的參與。