TFF Pharmaceuticals Inc (TFFP) 2023 Q2 法說會逐字稿

Good morning, Ladies and gentlemen, and welcome to the TFF Pharmaceuticals Second Quarter 2023 Corporate Update and Earnings Conference Call. As a reminder, this conference is being recorded.

早安，女士們、先生們，歡迎參加 TFF Pharmaceuticals 2023 年第二季公司最新動態與收益電話會議。提醒一下，本次會議正在錄製中。

I will now turn the call over to your host, Corey Davis of LifeSci Advisors. You may begin your conference.

我現在會把電話轉給主持人、LifeSci Advisors 的 Corey Davis。您可以開始您的會議了。

Thank you, operator. Hello, everyone, and welcome to TFF Pharmaceuticals Second Quarter 2023 Corporate Update and Earnings Conference Call. With me on the line this afternoon are Dr. Harlan Weisman, Chief Executive Officer of TFF Pharmaceuticals; Dr. Zamaneh Mikhak, Chief Medical Officer; and Kirk Coleman, Chief Financial Officer.

謝謝你，接線生。大家好，歡迎參加 TFF Pharmaceuticals 2023 年第二季公司更新與收益電話會議。今天下午與我通話的是 TFF Pharmaceuticals 執行長 Harlan Weisman 博士； Zamaneh Mikhak 博士，首席醫療官；和首席財務官柯克科爾曼。

Before we get started, I would like to remind everyone that this call will contain forward-looking statements, including, without limitation, statements about the anticipated timing of achievement of clinical milestones, the potential to see positive effects in our Phase II studies, the number of treated patients necessary to make our decisions in regards to moving to Phase III studies, the market opportunity for our product candidates and the expected timeframe for funding operations with cash and cash equivalents.

在我們開始之前，我想提醒大家，本次電話會議將包含前瞻性陳述，包括但不限於關於實現臨床里程碑的預期時間、在我們的 II 期研究中看到積極效果的潛力、我們做出有關進入III 期研究的決定所需的治療患者數量、我們的產品候選者的市場機會以及現金和現金等價物資助業務的預期時間範圍。

These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially from the statements made. Factors that could cause actual results to differ are described in all of our findings with the U.S. Securities and Exchange Commission, including the Risk Factors section of our 2022 annual report on Form 10-K filed with the SEC.

這些前瞻性陳述受到已知和未知的風險和不確定性的影響，可能導致實際結果與所做陳述有重大差異。我們向美國證券交易委員會提交的所有調查結果中描述了可能導致實際結果不同的因素，包括我們向 SEC 提交的 10-K 表格 2022 年年度報告中的風險因素部分。

And now it's my pleasure to turn the call over to Dr. Harlan Weisman. Harlan?

現在我很高興將電話轉給 Harlan Weisman 博士。哈倫？

Thank you, john, and good morning, everyone, and thank you for joining us for our second quarter 2023 Corporate Update and Earnings Conference Call. On today's call, I'm going to review the significant progress that we've made over the first half of 2023 and then provide an outlook on what we expect to achieve for the remainder of the year.

謝謝約翰，大家早上好，感謝您參加我們的 2023 年第二季公司最新動態和收益電話會議。在今天的電話會議上，我將回顧我們在 2023 年上半年取得的重大進展，然後展望我們預計在今年剩餘時間內實現的目標。

Following my remarks, our Chief Medical Officer; Dr. Zamaneh Mikhak will provide an update on TFFs clinical stage programs. Our Chief Financial Officer, Kirk Coleman, will then review our financial results for the second quarter. We'll then open up the call for Q&A.

在我發言之後，我們的首席醫療官； Zamaneh Mikhak 博士將提供 TFF 臨床階段計劃的最新資訊。我們的財務長柯克科爾曼隨後將審查我們第二季的財務表現。然後我們將開啟問答環節。

In early February, soon after my appointment as TFF's permanent CEO, we held an investor call to review our corporate strategy and outline our objectives for 2023. On that call, we expressed our commitment to grow shareholder value by prioritizing the advancement of our clinical stage assets, TFF VORI and TFS TAC. We also expressed a desire to remain opportunistic with respect to signing new partnerships that showed the potential to create long-term value while also minimizing internal costs to our company.

2 月初，在我被任命為TFF 永久執行長後不久，我們召開了一次投資者電話會議，審查我們的公司策略並概述我們的2023 年目標。在那次電話會議上，我們表達了通過優先推動臨床階段來增加股東價值的承諾資產、TFF VORI 和 TFS TAC。我們也表達了在簽署新合作夥伴關係方面保持機會主義的願望，這些合作關係顯示出創造長期價值的潛力，同時也最大限度地減少了我們公司的內部成本。

It's been nearly 6 months since that call, and I can say that I'm proud of the company's progress on both fronts. Under Zamaneh's leadership, our clinical development team has made considerable progress across a number of key areas to help build the physician and patient awareness of TFF VORI and TFF TAC. Based on the continued success of these efforts, we anticipate reaching key clinical milestones by year-end, each of which could serve as a major catalyst for our company. In a moment, Zamaneh will provide greater details on each of these rare disease programs.

距離那次電話會議已經過去近 6 個月了，我可以說我對公司在這兩方面的進展感到自豪。在 Zamaneh 的領導下，我們的臨床開發團隊在多個關鍵領域取得了長足進步，幫助增強醫生和患者對 TFF VORI 和 TFF TAC 的認識。基於這些努力的持續成功，我們預計到年底將達到關鍵的臨床里程碑，每個里程碑都可以成為我們公司的主要催化劑。稍後，紮馬內將提供有關這些罕見疾病項目的更多詳細資訊。

We will also have sufficient capital to reach these milestones. As announced earlier this morning, TFF raised additional capital through an equity financing. Importantly, no warrants were issued to investors in this transaction. Considering the ongoing challenges in the capital markets, our ability to close this financing while minimizing dilution to our existing shareholders, in my view, reflects a growing recognition of the attractive risk/reward of our 2 clinical programs. In contrast to programs involving new chemical entities, TFF VORI and TFF TAC, couple significant innovation with reduced clinical development risk. The innovation is driven, of course, by our Thin Film Freezing technology that enables efficacious levels of voriconazole and tacrolimus to be delivered directly into the lungs.

我們還將擁有足夠的資金來實現這些里程碑。正如今天早上早些時候宣布的，TFF 透過股權融資籌集了額外資金。重要的是，本次交易中沒有向投資者發行認股權證。考慮到資本市場持續面臨的挑戰，在我看來，我們能夠完成這項融資，同時最大限度地減少對現有股東的稀釋，反映出人們越來越認識到我們兩個臨床項目的吸引力的風險/回報。與涉及新化學實體的專案相比，TFF VORI 和 TFF TAC 將重大創新與降低的臨床開發風險結合起來。當然，這項創新是由我們的薄膜冷凍技術推動的，該技術能夠將有效水平的伏立康唑和他克莫司直接輸送到肺部。

Through this improved delivery, we expect to see strong efficacy, but with lower toxicity and drug-drug interactions compared to systemic delivery. Physicians have told us that they would welcome these types of solutions to improve overall care in these highly vulnerable patient populations. We also believe each program bears significantly less clinical risk compared to other development stage programs. By improving the delivery of 2 well-established first-line FDA-approved drugs, we expect to see positive treatment effects for most of the patients enrolling in our ongoing Phase II trials.

透過這種改進的遞送，我們期望看到強大的功效，但與全身遞送相比，毒性和藥物間相互作用更低。醫生告訴我們，他們歡迎這些類型的解決方案來改善這些高度脆弱的患者群體的整體護理。我們也相信，與其他開發階段的項目相比，每個項目的臨床風險要小得多。透過改善 2 種 FDA 批准的成熟一線藥物的輸送，我們預計大多數參加我們正在進行的 II 期試驗的患者都會看到積極的治療效果。

For this reason, I believe TFF represents a compelling opportunity for investors who seek an optimal balance of innovation, coupled with lower overall clinical development risk. Developing new therapies like TFF VORI and TFF TAC, that can efficiently deliver an effective drug while lowering systemic toxicities is likely to have a significant positive impact on overall patient health, clinical outcomes and health economics.

基於這個原因，我相信 TFF 對於尋求創新與較低整體臨床開發風險最佳平衡的投資者來說是一個極具吸引力的機會。開發 TFF VORI 和 TFF TAC 等新療法，可以有效地提供有效藥物，同時降低全身毒性，可能會對患者的整體健康、臨床結果和衛生經濟學產生重大的正面影響。

Given the size of the patient population, the level of unmet need, to the economic burden of each disease and the anticipated impact of TFF VORI and TFF TAC on clinical outcomes. We believe each product represents a $1 billion-plus market opportunity. While advancing our pipeline remains our primary strategic objective. I'm also pleased to note that business development at TFF remains quite active. We announced three separate government collaborations during the quarter, which provides third-party validation of the value of our Thin Film Freezing technology.

考慮到患者群體的規模、未滿足需求的程度、每種疾病的經濟負擔以及 TFF VORI 和 TFF TAC 對臨床結果的預期影響。我們相信每種產品都代表著價值超過 10 億美元的市場機會。雖然推進我們的管道仍然是我們的首要策略目標。我還很高興地註意到 TFF 的業務發展仍然相當活躍。我們在本季度宣布了三項獨立的政府合作，這為我們的薄膜冷凍技術的價值提供了第三方驗證。

In May, we signed a Cooperative Research and Development Agreement, or CRADA, with the National Institute of Environmental Health Sciences, part of the National Institutes of Health to develop dry powder formulations of Hyaluronan to prevent and treat respiratory diseases. NIEHS and TFF will evaluate the pharmacokinetics and therapeutic efficacy of TFF Hyaluronan formulations, using in vitro and in vivo models of select respiratory diseases with a primary focus on chronic obstructive pulmonary disease, or COPD, and viral respiratory diseases caused by SARS COV2, influenza virus and/or respiratory syncytial virus or RSV.

5 月，我們與美國國立衛生研究院下屬的國家環境健康科學研究所簽署了合作研究與開發協議 (CRADA)，開發用於預防和治療呼吸道疾病的透明質酸乾粉製劑。 NIEHS 和TFF 將使用選定呼吸系統疾病的體外和體內模型來評估TFF 透明質酸製劑的藥物動力學和治療效果，主要關注慢性阻塞性肺病(COPD) 以及SARS COV2、流感病毒引起的病毒性呼吸系統疾病和/或呼吸道合胞病毒或RSV。

Also in May, we signed a contract extension with Leidos that provides additional funding to advance next-generation personalized protective biosystems under the personalized protective Biosystems program managed by the Defense Advanced Research Projects Agency, more commonly referred to as DARPA. The goal of the program is to develop lightweight materials using Thin Film Freezing technology that protects military and healthcare personnel from exposure to chemical and biological threats.

同樣在5 月，我們與Leidos 簽署了一份延期合同，該合同提供額外資金，以在由國防高級研究計劃局（通常稱為DARPA）管理的個性化保護生物系統計劃下推進下一代個性化保護生物系統。該計劃的目標是利用薄膜冷凍技術開發輕質材料，保護軍事和醫護人員免受化學和生物威脅。

In June, we announced an agreement with the National Institute of Allergy and Infectious Diseases, also part of the National Institute of Health, that awarded TFF Pharmaceuticals, a direct to Phase II Small Business Innovation Research, or SBIR grant of approximately $3 million to continue development of a shelf-stable universal influenza mucosal vaccine using the company's Thin Film Freezing technology. The aim of this program is to develop a vaccine that is at least 75% effective against symptomatic influenza virus infection. Importantly, these agreements are largely funded by our partners, and provide an important source of external validation for our technology.

6 月，我們宣布與國家過敏和傳染病研究所（也是美國國立衛生研究院的一部分）達成協議，向 TFF Pharmaceuticals 授予約 300 萬美元的直接第二階段小型企業創新研究或 SBIR 撥款，以繼續進行利用該公司的薄膜冷凍技術開發一種耐儲存的通用流感黏膜疫苗。該計劃的目的是開發一種對有症狀的流感病毒感染有至少 75% 有效性的疫苗。重要的是，這些協議主要由我們的合作夥伴資助，並為我們的技術提供了外部驗證的重要來源。

I'd now like to turn the call over to Dr. Zamaneh Mikhak to discuss the TFF VORI and TFS TAC clinical programs. Zamaneh?

我現在想將電話轉給 Zamaneh Mikhak 博士，討論 TFF VORI 和 TFS TAC 臨床計劃。紮馬內？

Thank you, Harlan. As Harlan mentioned, I'm pleased to share with you the considerable progress we're making to advance enrollment in our 2 Phase II trials of TFF TAC and TFF VORI. Over the last several months, our clinical development team has undertaken multiple initiatives to advance these programs. I'll start by providing an update on TFF VORI. As a reminder, TFF VORI has been formulated using our Thin Film Freezing technology to deliver antifungal drug voriconazole directly to the lungs. TFF VORI is being developed for potential treatment of pulmonary fungal infections, including pulmonary aspergillosis, starting with invasive pulmonary aspergillosis or IPA.

謝謝你，哈蘭。正如 Harlan 所提到的，我很高興與您分享我們在推進 TFF TAC 和 TFF VORI 的 2 個 II 期試驗的註冊方面取得的巨大進展。在過去的幾個月裡，我們的臨床開發團隊採取了多項措施來推進這些專案。首先我將提供 TFF VORI 的最新情況。提醒一下，TFF VORI 是使用我們的薄膜冷凍技術配製的，可將抗真菌藥物伏立康唑直接輸送到肺部。 TFF VORI 正在開發用於潛在治療肺部真菌感染，包括肺麴菌病，首先是侵襲性肺麴菌病或 IPA。

IPA is a life-threatening fungal lung infection that primarily impacts immunocompromised patients. Even with standard of care therapy, the 12 week mortality rate from IPA is approximately 30%, which represents a significant unmet medical need for this rare disease. Oral voriconazole is first-line therapy for treatment of IPA, but because of the drug's narrow therapeutic window, attaining efficacious concentrations often requires dosages that cause significant toxicities.

IPA 是一種危及生命的真菌肺部感染，主要影響免疫功能低下的患者。即使採用標準護理治療，IPA 12 週死亡率約為 30%，這表明這種罕見疾病的醫療需求尚未得到滿足。口服伏立康唑是治療 IPA 的第一線療法，但由於該藥物的治療窗較窄，因此要達到有效濃度通常需要引起顯著毒性的劑量。

By administering TFF VORI directly into the lungs, we hope to improve efficacy by delivering high local concentrations of the drug, while lowering systemic exposures and, therefore, systemic toxicities and drug-drug interactions, problems commonly associated with oral administration. As Harlan mentioned earlier, we have made considerable progress over the last several months. We established weekly goals for our CRO and weekly meetings with CRO upper management, to improve accountability and overall execution, and these changes have helped considerably. For example, we now have 16 of our 19 clinical sites activated compared to only a single site when I first joined TFF back in January. We expect additional sites to be up and running this quarter.

透過將 TFF VORI 直接注入肺部，我們希望透過提供高局部藥物濃度來提高療效，同時降低全身暴露，從而降低全身毒性和藥物間相互作用，這些問題通常與口服給藥相關。正如哈倫之前提到的，我們在過去幾個月中取得了相當大的進展。我們為 CRO 制定了每週目標，並與 CRO 高階主管每週舉行會議，以提高問責制和整體執行力，這些變化起了很大作用。例如，我們現在已經啟動了 19 個臨床中心中的 16 個，而我一月份第一次加入 TFF 時只有一個中心被啟動。我們預計本季將有更多站點啟動並運行。

The variance of the TFF VORI program is growing among hematologists, oncologists, infectious disease physicians, pulmonologists and transplant physicians as our active clinical sites and their referral networks, which in turn is leading to an acceleration in patient prescreening and screening activities. As a result, our [radar] prescreening has increased nearly fivefold in the past four months compared to the first four months from 9 to 44. And we now have 2 patients enrolled in our study.

作為我們活躍的臨床中心及其轉診網絡，TFF VORI 計劃在血液科醫生、腫瘤科醫生、傳染病醫生、肺科醫生和移植醫生之間的差異正在不斷擴大，這反過來又加速了患者預篩檢和篩檢活動。因此，我們的[雷達]預篩檢在過去四個月中比前四個月增加了近五倍，從 9 到 44。現在我們有 2 名患者參加了我們的研究。

Additionally, we have amended the study protocol to improve patient access to TFF VORI. For example, based on feedback from our investigators, we have expanded eligibility to allow real world criteria used for the diagnosis of IPA. In a disease with high unmet need, in which first-line therapy is associated with high mortality, toxicity and drug-drug interactions, patients often choose to participate in a clinical trial with the hope of receiving an investigational drug with potential for improved efficacy and toxicity. To improve the chances of receiving TFF VORI, we have also increased the ratio of patients receiving TFF VORI to those receiving oral voriconazole from 1:1 to 3:1 in this study.

此外，我們也修改了研究方案，以改善患者獲得 TFF VORI 的機會。例如，根據研究人員的回饋，我們擴大了資格，允許使用現實世界的標準來診斷 IPA。在一種需求未被滿足的疾病中，第一線治療與高死亡率、毒性和藥物間相互作用相關，患者通常選擇參加臨床試驗，希望接受一種有可能提高療效和療效的研究藥物。毒性。為了提高接受 TFF VORI 的機會，我們在本研究中也將接受 TFF VORI 的患者與接受口服伏立康唑的患者的比例從 1:1 增加至 3:1。

While we're developing TFF VORI for the potential treatment of IPA by conducting clinical trials, we understand that in some cases, patients who have exhausted available therapeutic options may not qualify for participation in clinical trials. For such cases, we have launched an expanded access program, or EAP, offering TFF VORI to patients with all forms of pulmonary aspergillosis, including both invasive and chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, Aspergillus Tracheobronchitis and aspergillus bronchial anastomotic infections.

雖然我們正在透過臨床試驗開發 TFF VORI 以用於 IPA 的潛在治療，但我們了解，在某些情況下，用盡可用治療方案的患者可能沒有資格參加臨床試驗。針對此類病例，我們啟動了一項擴大准入計劃（EAP），為患有各種形式肺曲霉病的患者提供TFF VORI，包括侵襲性和慢性肺曲霉病、過敏性支氣管肺曲霉病、曲霉氣管支氣管炎和麴菌支氣管吻合口感染。

Patients with other voriconazole responsive pulmonary infections also qualified for this program. The patients who enter our EAP have limited or no treatment options or in some cases, have had an unfavorable response to standard of care therapy. The EAP program builds on the positive efficacy, safety and tolerability results in 2 such patients with pulmonary fungal infections who were previously treated with TFF VORI on a compassionate use basis.

患有其他伏立康唑反應性肺部感染的患者也符合該計劃的資格。進入我們 EAP 的患者的治療選擇有限或沒有，或者在某些情況下，對標準護理治療反應不佳。 EAP 計劃建立在 2 名肺部真菌感染患者的積極療效、安全性和耐受性結果的基礎上，這些患者之前在同情使用的基礎上接受過 TFF VORI 治療。

I'm also pleased to note our collaboration with Durbin to help us implement the EAP for TFF VORI in the U.S. Canada, Australia, U.K. and select countries in the EU. Durbin has a long track record of executing expanded access programs across the globe for large and small pharma companies, and we are confident that through this partnership, we will be able to provide expanded access to TFF VORI to eligible patients. In fact, I'm pleased to note that we have already enrolled our first patient in this new program. As Harlan mentioned, we expect to see a majority of patients who receive TFF VORI therapy to show a positive treatment effect due to the well-established activity of voriconazole as an antifungal medication.

我還很高興地註意到我們與 Durbin 的合作，幫助我們在美國、加拿大、澳洲、英國和部分歐盟國家實施 TFF VORI EAP。德賓在全球範圍內為大型和小型製藥公司執行擴大准入計劃方面有著悠久的記錄，我們相信，透過這種合作夥伴關係，我們將能夠為符合條件的患者提供 TFF VORI 的擴大准入機會。事實上，我很高興地註意到，我們已經在這個新計劃中招募了第一位患者。正如 Harlan 所提到的，由於伏立康唑作為抗真菌藥物的公認活性，我們預計大多數接受 TFF VORI 治療的患者會表現出積極的治療效果。

Given the availability of considerable historical data on the safety, tolerability and efficacy of voriconazole, and in line with what is generally customary in rare disease indications, we believe no more than 10 patients treated with TFF VORI may be necessary to provide us with enough clinical data to make a Go/No Go decision on entering the Phase III trial. Initial data from our ongoing Phase II trial in EAP are expected by the end of 2023.

鑑於關於伏立康唑的安全性、耐受性和有效性的大量歷史數據的可用性，並且符合罕見疾病適應症的通常慣例，我們相信可能需要不超過10 名接受TFF VORI 治療的患者來為我們提供足夠的臨床數據。數據以做出是否進入 III 期試驗的決定。我們正在進行的 EAP II 期試驗的初步數據預計將於 2023 年底獲得。

Now let me turn to discussing the TFF TACs Phase II program. Similar to TFF VORI, the TFF TAC program addresses an area of significant unmet medical need in another rare disease indication. TFF TAC is being developed for prevention of rejection in lung transplant recipients, a patient population with 5-year mortality rate as high as 50%. The 50% 5-year mortality in lung transplant comes largely from the narrow therapeutic window of available immunosuppressants where too little immunosuppression leads to acute or chronic rejection, whereas too much immune suppression leads to infection, chronic kidney disease and post-transplant lymphoma other malignancies.

現在讓我談談 TFF TAC 第二階段計劃。與 TFF VORI 類似，TFF TAC 計劃解決了另一個罕見疾病適應症中未滿足的重大醫療需求領域。 TFF TAC 正在開發用於預防肺移植受者的排斥反應，該患者群體的 5 年死亡率高達 50%。肺移植中50% 的5 年死亡率主要是由於可用免疫抑制劑的治療窗狹窄，免疫抑制太少會導致急性或慢性排斥反應，而免疫抑制太多會導致感染、慢性腎臟病和移植後淋巴瘤和其他惡性腫瘤。

To overcome these efficiencies TFF TAC has been formulated using our Thin Film Freezing technology to deliver the first-line calcineurin inhibitor immunosuppressant drug tacrolimus directly to the lungs. The direct delivery of TFF TAC to the lungs is poised to potentially address multiple contributing factors to the 50% 5-year mortality being in lung transplant. With local delivery to the lung, the ratio of lung exposure to systemic exposure increases. Therefore, lung concentration is sufficient to drive efficacy locally can be achieved at lower doses compared to oral administration leading to lower systemic exposures to minimize systemic toxicity.

為了克服這些效率，TFF TAC 採用我們的薄膜冷凍技術配製，將一線鈣調神經磷酸酶抑制劑免疫抑制劑藥物他克莫司直接輸送到肺部。將 TFF TAC 直接輸送到肺部有望解決肺移植中導致 50% 5 年死亡率的多種影響因素。隨著局部遞送至肺部，肺部暴露與全身暴露的比率增加。因此，與口服給藥相比，肺濃度足以驅動局部療效，可以在較低劑量下實現局部療效，從而導致較低的全身暴露，從而最大限度地減少全身毒性。

The improved lung to systemic exposure achieved with TFF TAC is predicted to address the fine balance needed for immunosuppression. The improved concentrations in the lung, the site of inflammation would address acute and chronic rejection, while diminished systemic exposures would address potentially fatal complications, such as infections, chronic kidney disease and post-transplant lymphoma or other malignancies.

TFF TAC 改善了肺部與全身的暴露，預計將解決免疫抑制所需的精細平衡。肺部（發炎部位）濃度的提高將解決急性和慢性排斥反應，而全身暴露的減少將解決潛在的致命併發症，例如感染、慢性腎臟病和移植後淋巴瘤或其他惡性腫瘤。

It should be noted that presence of systemic exposure, albeit at lower levels compared to oral tacrolimus is predicted to suppress systemic inflammation to further prevent rejection. In our Phase II trial, we have gained considerable insights at our active site in Australia in transitioning lung transplant patients from oral tacrolimus to the inhaled form TFF TAC. The transition from oral to inhale tacrolimus is a delicate process given the risk of rejection and toxicity. We have been presently surprised by the low doses of TFF TAC needed to date, to match overall clinical outcomes from oral tacrolimus.

應該指出的是，全身暴露的存在，儘管與口服他克莫司相比水平較低，預計會抑制全身炎症，進一步防止排斥反應。在我們的 II 期試驗中，我們在澳洲的活動中心獲得了相當多的見解，幫助肺移植患者從口服他克莫司過渡到吸入形式的 TFF TAC。考慮到排斥和毒性的風險，從口服他克莫司到吸入他克莫司的過渡是一個微妙的過程。目前，我們對迄今為止所需的低劑量 TFF TAC 感到驚訝，以匹配口服他克莫司的整體臨床結果。

To date, three patients have enrolled in the Phase II study at our active site. We expect to activate additional sites in Australia in the coming months. Since our selected sites have a large database of lung transplant patients that could be considered for potential enrollment in our study, we expect a steady flow of patients in our TFF TAC study. Similar to the TFF VORI program, given the availability of considerable historical data on the safety, tolerability and efficacy of tacrolimus, and in line with what is general practice in rare indications, we believe meaningful clinical data from approximately 10 patients treated with TFF TAC will be sufficient to guide a Go/No Go decision for entering a Phase III study, and we expect to report initial data from the ongoing Phase II study by the end of 2023.

迄今為止，已有三名患者參加了我們活動中心的 II 期研究。我們預計未來幾個月將在澳洲啟動更多站點。由於我們選擇的地點擁有大型肺移植患者資料庫，可以考慮將其納入我們的研究中，因此我們預計 TFF TAC 研究中的患者會有穩定的流動。與TFF VORI 計劃類似，考慮到有關他克莫司的安全性、耐受性和有效性的大量歷史數據，並且符合罕見適應症的一般實踐，我們相信來自約10 名接受TFF TAC 治療的患者的有意義的臨床數據將足以指導進入 III 期研究的進行/不進行決定，我們預計在 2023 年底之前報告正在進行的 II 期研究的初步數據。

I'll now turn the call over to Kirk to review our second quarter financial results.

我現在將把電話轉給柯克，以審查我們第二季的財務表現。

Thanks very much, Zamaneh. Our cash and cash equivalents as of June 30, 2023, were $7.7 million. The additional proceeds from the financing transaction announced earlier today, will ensure that we have sufficient resources to reach anticipated upcoming clinical milestones and will extend our cash runway through the first quarter of 2024. The Research and development expenses for the second quarter of 2023 were $2.7 million compared to $5.1 million for the comparable period in 2022. $2.4 million decrease year-over-year is primarily a result of reduced clinical and manufacturing expenses.

非常感謝，紮馬內赫。截至 2023 年 6 月 30 日，我們的現金和現金等價物為 770 萬美元。今天稍早宣布的融資交易的額外收益將確保我們有足夠的資源來實現預期的即將到來的臨床里程碑，並將我們的現金跑道延長到2024 年第一季。2023 年第二季的研發費用為2.7 美元2022 年同期為 510 萬美元。年減 240 萬美元主要是由於臨床和製造費用減少。

General administrative expenses for the second quarter of 2023 were $2.7 million compared to $3.7 million for the comparable period in 2022. $1 million decrease year-over-year is primarily related to decreased professional fees and patent expenses, insurance, consulting, market research and payroll and payroll-related expenses. Net loss for the second quarter of 2023 of $5 million compared to a net loss of $8.7 million for the comparable period in 2022. [To all] noted previously, we have been focused on spending responsibly as we progress our clinical trial programs. I'm proud of the team for successfully reducing spending in areas that were not part of the primary strategic objectives. I'll now turn the call back over to Harlan.

2023 年第二季的一般管理費用為 270 萬美元，而 2022 年同期為 370 萬美元。年減 100 萬美元，主要與專業費用和專利費用、保險、諮詢、市場研究和工資的減少有關以及與工資相關的費用。 2023 年第二季的淨虧損為 500 萬美元，而 2022 年同期的淨虧損為 870 萬美元。[致所有人]之前指出，在推進臨床試驗計畫時，我們一直致力於負責任地支出。我為團隊成功減少了不屬於主要策略目標的領域的支出感到自豪。我現在將把電話轉回給哈倫。

Thank you, Kirk. Before opening up the call for questions, I would like to express my sincere thanks to Zamaneh and her team for all of their hard work and dedication, which has enabled us to make significant progress across multiple fronts in our TFF TAC and TFF VORI program. Since becoming CEO 6 months ago, my confidence in the therapeutic and commercial value of these two assets has only continued to grow. By improving drug delivery with our thin Film Freezing Technology, the VORI and TAC programs have the potential to demonstrate a transformative impact in 2 rare disease indications by effectively restoring the full efficacy potential of life-saving medicines.

謝謝你，柯克。在開始提問之前，我要對 Zamaneh 和她的團隊的辛勤工作和奉獻精神表示誠摯的感謝，他們使我們能夠在 TFF TAC 和 TFF VORI 項目的多個方面取得重大進展。自從 6 個月前成為執行長以來，我對這兩項資產的治療和商業價值的信心不斷增強。透過利用我們的薄膜冷凍技術改善藥物輸送，VORI 和 TAC 計畫有可能透過有效恢復救命藥物的全部功效潛力，對 2 種罕見疾病適應症產生變革性影響。

Moreover, each addresses areas of significant unmet medical need in rare disease indications, with sizable patient populations and substantial market opportunity. If we succeed in this endeavor, I'm equally confident that the value of our technology platform, internal pipeline and partnerships will be increasingly recognized in the market, providing investors with the opportunity to reassess the value of our company in the months ahead.

此外，每個項目都解決了罕見疾病適應症中未滿足的重大醫療需求領域，擁有大量患者群體和巨大的市場機會。如果我們在這項努力中取得成功，我同樣相信我們的技術平台、內部管道和合作夥伴關係的價值將越來越得到市場的認可，為投資者提供在未來幾個月重新評估我們公司價值的機會。

That concludes our formal remarks, and I'd like now to open the call up for the question-and-answer session. Operator?

我們的正式演講到此結束，現在我想開始問答環節。操作員？

(Operator Instructions) First question comes from Jonathan Aschoff of ROTH MKM.

（操作員說明）第一個問題來自 ROTH MKM 的 Jonathan Aschoff。

My first question, guys, is about VORI, given that there's only 2 patients in the trial, what gives you the confidence that you can meet that 10-patient expectation by year-end. And I guess this explains the 2:1 ratio of sites to intended patients.

各位，我的第一個問題是關於 VORI 的，鑑於試驗中只有 2 名患者，是什麼讓你們有信心在年底前達到 10 名患者的預期。我想這可以解釋為什麼站點與目標患者的比例為 2:1。

Jonathan, thank you for the question. The clinical trial has been ramping up since Zamaneh took over as Chief Medical Officer. And it is a process that takes a while to overcome the initial inertia in the clinical trial. But we're now, as Zamaneh went over in her remarks, seeing that progress. And I'll ask Zamaneh to comment further on answering your question.

喬納森，謝謝你的提問。自 Zamaneh 接任首席醫療官以來，臨床試驗一直在加速。而克服臨床試驗最初的慣性是一個需要一段時間的過程。但正如紮馬內赫在她的演講中所說，我們現在看到了這一進展。我將請 Zamaneh 進一步評論回答你的問題。

Jonathan, thanks for the question. As I mentioned, we have made a significant level of progress. We now have 80% of our sites activated, 16 sites in Europe in 5 different countries. Our investigators are engaged, our protocol eligibility has been expanded to allow patients that need real-life criteria for diagnosis of IPA. And because we've changed the randomization schedule such that instead of 1 to 1, patients have the opportunity to receive TFF VORI with a 3:1 chance. The trial is a lot more inviting to patients who would consider participation. All of this momentum, we believe is setting us up to bring the number of patients that we are projecting and to have initial data by the end of the year.

喬納森，謝謝你的提問。正如我所提到的，我們已經取得了顯著的進展。目前，我們 80% 的站點已激活，其中 16 個站點位於歐洲 5 個不同國家。我們的研究人員積極參與，我們的方案資格已擴大到允許需要現實生活中 IPA 診斷標準的患者。因為我們改變了隨機化時間表，患者有機會以 3:1 的機會接受 TFF VORI，而不是 1 比 1。該試驗對考慮參與的患者更具吸引力。我們相信，所有這些勢頭將使我們能夠在年底前獲得我們預測的患者數量並獲得初步數據。

With the -- the hype [created], can you tell me, I mean, you're up fivefold in the past 4 months, but to only have 2 patients, what's the explanation for so few patients qualifying for this trial?

隨著——[創造]的炒作，你能告訴我，我的意思是，你在過去4 個月裡增長了五倍，但只有2 名患者，為什麼有資格參加這項試驗的患者如此之少？

That's a good question. IPA is a fatal disease. So 1 of the things that we're noticing is that because it's such a severe disease, you have severe fungal infection on top of, for example, hematologic malignancy. This is a patient, say, with leukemia, type of leukemia, who now has a fungal infection, so quite a fatal disease. What we've noticed is that many of the patients who are considered for the clinical trial actually end up in hospice or palliative care. They're quite ill and that's why they don't qualify.

這是個好問題。 IPA是一種致命的疾病。因此，我們注意到的一件事是，因為這是一種如此嚴重的疾病，所以除了血液惡性腫瘤之外，還有嚴重的真菌感染。比如說，這是一名患有白血病的患者，這種白血病的類型，現在患有真菌感染，因此是一種致命的疾病。我們注意到，許多被考慮參加臨床試驗的患者實際上最終接受了臨終關懷或安寧療護。他們病得很重，這就是他們沒有資格的原因。

Another reason that they might not qualify is that the diagnosis ends up not being aspergillus or not being exactly IPA or they're not meeting the very specific and very narrow criteria for diagnosis of IPA based on the original diagnostic criteria that was in the protocol, which we've capped, but again, we expanded that to include real-life criteria, and we believe that improves eligibility and study participation. As I mentioned, we have a lot of sites active now and the investigators are quite engaged. But at the end of the day, we want to make sure we get the right patients in this study.

他們可能不合格的另一個原因是，診斷最終不是曲霉菌或不完全是 IPA，或者他們不符合基於方案中原始診斷標準的非常具體且非常狹窄的 IPA 診斷標準，我們已經對此進行了限制，但我們再次將其擴展為包括現實生活中的標準，我們相信這會提高資格和研究參與。正如我所提到的，我們現在有很多活躍的網站，調查人員也非常投入。但歸根結底，我們希望確保在這項研究中找到合適的患者。

And I think the other thing to really keep in mind is that what do you accomplish, what can you accomplish while you're setting things up? And what can you accomplish once you have set things up. So we have brought in the number of patients that we brought in as we've been activating sites, as we've been putting in an addendum, as we've been putting in an amendment. But doing that requires a lot of steps to actually implement these changes.

我認為另一件需要真正記住的事情是，當你設定事情時，你會完成什麼，你能完成什麼？一旦你把事情做好了，你能完成什麼？因此，我們已經引入了我們引入的患者數量，因為我們一直在啟動站點，因為我們一直在添加附錄，因為我們一直在添加修正案。但要做到這一點需要採取很多步驟來實際實施這些改變。

Now we're at a point where the sites are active. The amendment is in place and approved in almost every country. The sites are familiar with these broadened eligibility criteria, and they understand how that impacts their evaluation of patients. So that's why looking at the activities on the ground and the information we have, we're comfortable to project that we'll be able to have initial data by the year-end.

現在我們正處於站點活躍的階段。該修正案已在幾乎每個國家實施並獲得批准。這些網站熟悉這些擴大的資格標準，並且了解這如何影響他們對患者的評估。因此，根據實地活動和我們掌握的信息，我們很高興地預測我們將能夠在年底前獲得初步數據。

What was flawed about 40 patients as an enrollment number for VORI such that, 10 can allow you to come up with a go/no-go decision for Phase III?

VORI 的入組人數為 40 名患者，這有什麼缺陷，以至於 10 名患者可以讓您對 III 期做出進行/不進行的決定？

That's a good question, too. The 40-patient trial was the original design of this study really did not take into account that the indication, IPA is a rare disease. You do a 40-patient Phase II study, for example, in rheumatoid arthritis, if you're doing a sort of a regular park or you do it in psoriasis, big, common -- big footprint disease. In rare diseases, generally, you look for a smaller sample size in your trials because there are just much fewer patients in these trials. For example, IPA, the number of patients with new diagnosis of IPA worldwide is 80,000 patients. So that's quite a rare disease.

這也是個好問題。這項40名患者的試驗最初的設計確實沒有考慮到IPA是一種罕見疾病的適應症。例如，如果您正在做常規公園的類風濕性關節炎，或者您正在針對銀屑病（一種大的、常見的大足跡疾病）進行一項包含 40 名患者的 II 期研究。一般來說，在罕見疾病中，您會在試驗中尋找較小的樣本量，因為這些試驗中的患者要少得多。例如IPA，全球新診斷IPA的患者數為8萬名。所以這是一種相當罕見的疾病。

So the way one does clinical development in a rare disease indication is that you look for more telling signals of efficacy, and that helps you have a smaller sample size. We also have the luxury that the drug redeveloping for first-line approved drugs, the chemical entities are not new. So we know what voriconazole can do. We know what tacrolimus can do. We understand their efficacy profile. We understand their safety and tolerability profile. So we don't think you need 40 patients to be able to make a call as to how TFF VORI doing compared to oral voriconazole.

因此，在罕見疾病適應症中進行臨床開發的方式是尋找更有說服力的療效訊號，這有助於您獲得較小的樣本量。我們還有幸的是，第一線核准藥物的藥物再開發，化學實體並不新鮮。所以我們知道伏立康唑可以做什麼。我們知道他克莫司可以做什麼。我們了解他們的功效概況。我們了解它們的安全性和耐受性概況。因此，我們認為不需要 40 名患者就能了解 TFF VORI 與口服伏立康唑相比效果如何。

I'll give you an example. With oral voriconazole, about 15% to 20% of patients have to decrease their dose or actually eventually go off therapy because of liver toxicity. That's a really high rate of liver toxicity, and that's very well known, very common experience. In our clinical trials, we have not seen any patients so far between the healthy volunteers, between patients with mild asthma, between the patients we've had in compassionate use, between the patients we've had so far in our clinical trial, nobody with liver toxicity.

我給你舉個例子。對於口服伏立康唑，大約 15% 至 20% 的患者必須減少劑量，或因肝毒性而最終停止治療。這是一個非常高的肝毒性發生率，這是眾所周知、非常普遍的經驗。在我們的臨床試驗中，到目前為止，在健康志願者之間、在輕度氣喘患者之間、在我們同情使用的患者之間、在我們臨床試驗中迄今為止接觸過的患者之間，我們還沒有看到任何患者。具有肝毒性。

So we don't think you're going to need 40 patients to be able to make this call, the difference will be large enough that you'll be able to make it call with just 10 patients. So it's really an adjustment in clinical trials designed to match the indication a little bit better?

因此，我們認為您不需要 40 名患者才能撥打此電話，差異將足夠大，您只需 10 名患者即可撥打電話。那麼這真的是臨床試驗的調整，旨在更好地匹配適應症嗎？

Okay. So you will make that decision on 10 patients versus 10 doesn't quite look compelling, hey let's enroll more. Like what do you think you're more likely to do, just make that call? Or if that's not clearly a yes, try for some more patients to see if it gets to a yes?

好的。因此，您將針對 10 名患者做出決定，而 10 名患者看起來不太令人信服，嘿，讓我們招募更多患者。例如你認為你更有可能做什麼，直接打電話？或者，如果這還不是明確的答案，請嘗試更多的患者，看看是否會得到答案？

We've always said it's approximately 10 patients. But bottom line is that we don't think you need a lot more than that. Obviously, you have to look at your data, make decisions accordingly, but we don't think it will be -- you need the original design, which was comparing 20 patients getting TFF VORI with 20 patients getting oral voriconazole and then making a call. We think we'll be able to really rely and draw on the experience that the knowledge that's there about oral voriconazole, and also you would need fewer patients than 20 to make a call about TFF VORI.

我們總是說大約有 10 名患者。但最重要的是，我們認為您不需要更多。顯然，你必須查看數據，做出相應的決定，但我們認為不會——你需要原始設計，該設計將 20 名接受 TFF VORI 的患者與 20 名接受口服伏立康唑的患者進行比較，然後打電話。我們認為我們將能夠真正依賴和借鑒有關口服伏立康唑的知識的經驗，而且您需要的患者數量少於 20 名才能撥打有關 TFF VORI 的電話。

Okay, and I'll not leave Kirk out. Kirk there were sequential decreases, which is good in R&D and SG&A for the first and the second quarter. Are you at a cruising altitude, or do you expect that to continue dropping a little?

好吧，我不會把柯克排除在外。 Kirk 出現連續下降，這在第一季和第二季的研發和銷售、一般管理費用方面表現良好。您是否處於巡航高度，或者您預計該高度會繼續下降嗎？

That's a great question, Jonathan. I think we are starting to settle in and the guidance we're giving, obviously, is we're anticipating that our burn rate is about $4 million a quarter, and we've got enough runway to get us through into Q1 of 2024.

這是一個很好的問題，喬納森。我認為我們已經開始適應，顯然我們給出的指導是我們預計每季度的燒錢率約為 400 萬美元，並且我們有足夠的跑道讓我們度過 2024 年第一季。

The next question comes from Justin Walsh of JonesTrading.

下一個問題來自 JonesTrading 的 Justin Walsh。

Can you expand on your criteria you expect to use for your go/no-go decisions. Like what type of results would you need to see to give you confidence that it warrants advancing into phase III for either asset?

您能否詳細闡述您期望用於做出是否繼續決策的標準？例如，您需要看到什麼類型的結果才能讓您確信任一資產值得進入第三階段？

Justin, thank you for the question. That 1 seems like another perfect one for Zamaneh to address.

賈斯汀，謝謝你的提問。這個 1 似乎是 Zamaneh 需要解決的另一個完美問題。

Thank you, Justin. So we will look at signals of efficacy. For example, in TFF VORI, we certainly want to see that patients are feeling better. The clinical signs and symptoms have improved, and we like to see that there is evidence that Aspergillus has been cleared. The treatment duration is about 12 weeks. That may or may not be long enough to see radiologic evidence, but we certainly look for it, and we expect to see that at least in some patients. In the TFF TAC program, for example, we want to make sure that as we transition patients from the oral tacrolimus to the inhale tacrolimus, we continue to see that TAC patients are free of rejection. And that they have shown good signs of safety and tolerability. And of course safety and tolerability is big for TFF VORI as well.

謝謝你，賈斯汀。因此，我們將關注功效訊號。例如，在 TFF VORI 中，我們當然希望看到患者感覺更好。臨床徵兆和症狀有所改善，我們希望看到有證據表明曲霉菌已被清除。治療時間約12週。這可能或可能不足以看到放射學證據，但我們肯定會尋找它，並且我們期望至少在某些患者中看到這一點。例如，在 TFF TAC 計畫中，我們希望確保當我們將患者從口服他克莫司過渡到吸入他克莫司時，我們繼續看到 TAC 患者不會出現排斥反應。並且它們已經顯示出良好的安全性和耐受性跡象。當然，安全性和耐受性對於 TFF VORI 也很重要。

And did you have discussions with the FDA or the EMA related to the amendment of the trial?

您是否與 FDA 或 EMA 就試驗修改進行過討論？

We made the amendment, and we submitted it to the health authorities in the various countries we're in, in Europe, and they've been approved in 4 out of 5 countries, and it's under review in the fifth country.

我們進行了修訂，並將其提交給我們所在的歐洲各國的衛生當局，它們已在五分之四的國家獲得批准，並且正在第五個國家進行審查。

And then last question for me, You had mentioned the hospice and some of that angle here. But I'm just wondering if you can remind us or provide commentary on the expanded access and compassionate use of TFF VORI. What alternatives do these patients face, either in terms of standard of care or other experimental therapies that you might be aware of?

然後問我的最後一個問題，你在這裡提到了臨終關懷和一些這個角度。但我只是想知道您是否可以提醒我們或對 TFF VORI 的擴大訪問和同情使用提供評論。這些患者面臨哪些替代方案，無論是標準護理還是您可能知道的其他實驗療法？

So the expanded access program really provides the opportunity for patients who might benefit from TFF VORI to get access to it. And the patients who might benefit from this therapy are not just patients who have invasive pulmonary aspergillosis. There are many other indications for which TFF VORI could be helpful. Chronic pulmonary aspergillosis, ABPA in patients with lung transplant broncho anastomotic infections, there are many areas and also fungal infections that are not aspergillus but they are voriconazole sensitive.

因此，擴大訪問計劃確實為可能受益於 TFF VORI 的患者提供了獲得該服務的機會。可能從這種療法中受益的患者不僅僅是患有侵襲性肺麴菌病的患者。 TFF VORI 對許多其他適應症也有幫助。慢性肺部麴菌病、ABPA肺移植患者支氣管吻合口感染，有許多部位也有非麴菌但對伏立康唑敏感的黴菌感染。

So every time you do a clinical trial and you have a clinical trial protocol, you have to implement and cement a particular design. And once that design is cemented, then there are patients who don't qualify based on 1 thing or another. So the expanded access program really helps us get TFF VORI in the hands of patients who could potentially benefit from it. And these are patients, like you mentioned, who have tried standard-of-care therapy at adequate levels and they have not had a good response to it or because of systemic toxicities are not able to tolerate these drugs.

因此，每次進行臨床試驗並制定臨床試驗方案時，您都必須實施並鞏固特定的設計。一旦這個設計得到鞏固，就會有一些患者因為這樣或那樣的原因而不符合資格。因此，擴大准入計畫確實有助於我們將 TFF VORI 交到可能從中受益的患者手中。正如您所提到的，這些患者已經嘗試過足夠的標準護理治療，但沒有產生良好的反應，或者由於全身毒性而無法耐受這些藥物。

The 2 patients we had for compassionate use that were treated previously. For example, were patients who were lung transplant recipients, they had recurrent pulmonary infections, pulmonary fungal infections. And they had significant toxicities to the point that when their infection came back, they were at the end of their rope. And didn't have -- didn't know where to go, and that's when TFF VORI was given to them with very good results.

我們出於同情心使用的 2 名患者之前接受過治療。例如，肺移植患者會反覆出現肺部感染、肺部真菌感染。而且它們具有顯著的毒性，以至於當它們再次感染時，它們已經到了窮途末路的地步。並且沒有--我不知道該去哪裡，就在那時，TFF VORI 被給予了他們，並取得了非常好的效果。

The next question comes from Vernon Bernardino from H.C. Wainwright.

下一個問題來自 H.C. 的 Vernon Bernardino。溫賴特。

Your answers as far as the VORI program have been very informative. So I think I know the answer to my question. Regarding the Phase II TFF TAC program, though, do you think that the small number of patients that are going to be dosed with the -- in the TAC clinical trial will be predicted enough to also make a go/no-go decision for Phase III?

您對 VORI 計劃的回答非常豐富。所以我想我知道我的問題的答案。不過，關於 II 期 TFF TAC 計劃，您是否認為 TAC 臨床試驗中將接受劑量的少數患者足以預測到是否可以對第二階段做出進行/不進行的決定？三世？

Why don't you go ahead and take that, Zamaneh.

為什麼不繼續接受這個呢，Zamaneh。

Yes. Yes, we think just about 10 patients would be sufficient for us to make a call about TFF TAC as well. As I mentioned, we've enrolled 3 patients, with our first patient, it was the first time we were transitioning patients from oral tacrolimus to inhale tacrolimus. So we approached this very conservatively, watching that patient very carefully, making the transition and then very slowly weaning that dose of inhaled tacrolimus because you have to have -- you have to be careful about that balance of making sure the patients have been going to rejection while you're improving prospects of safety and tolerability.

是的。是的，我們認為大約 10 名患者就足以讓我們就 TFF TAC 進行電話諮詢。正如我所提到的，我們已經招募了 3 名患者，其中第一位患者是我們第一次將患者從口服他克莫司過渡到吸入他克莫司。因此，我們非常保守地處理這個問題，非常仔細地觀察該患者，進行過渡，然後非常緩慢地戒掉吸入他克莫司的劑量，因為你必須 - 你必須小心確保患者一直要接受的平衡拒絕，同時您正在改善安全性和耐受性的前景。

And we -- as I mentioned we were surprised of how low we were able to go in the TFF TAC dose. With the second patient, we implemented our learnings from the first patient, we were able to duplicate those observations. So obviously, we want to see that happening in a number of other patients, but we think 10 -- approximately 10 patients will be sufficient to give us the information we need to make a call that, yes, this is a Go into Phase III. And obviously, you continue always to learn from additional patients you bring in, all throughout your development program, but approximately 10 patients should be sufficient.

正如我所提到的，我們對 TFF TAC 劑量的降低程度感到驚訝。對於第二位患者，我們實施了從第一位患者學到的知識，我們能夠重複這些觀察結果。顯然，我們希望看到這種情況發生在許多其他患者身上，但我們認為10 名——大約10 名患者就足以向我們提供所需的信息，以便我們做出決定，是的，這是進入III期臨床試驗。顯然，在整個開發計劃中，您始終會向引入的其他患者學習，但大約 10 名患者就足夠了。

Great, I look forward to that decision. Now I know an expanded access program is generally not one designed to provide results, for example. But the expanded access program, especially with your drugs, TFF VORI and TAC, in particular, the voriconazole study as you mentioned, the small number of patients, would there be a possibility to get any kind of data and/or results from that program and would especially with the help of Durbin Ireland or Uniphar rather provide -- perhaps broad coverage of the kind of patients globally that you could I guess, put together, translate, synthesize however you want to describe it into the results that you might see with TFF VORI?

太好了，我期待這個決定。例如，現在我知道擴展訪問計劃通常不是旨在提供結果的計劃。但擴大准入計劃，特別是您的藥物、TFF VORI 和 TAC，特別是您提到的伏立康唑研究，患者數量較少，是否有可能從該計劃中獲得任何類型的數據和/或結果尤其是在Durbin Ireland 或Uniphar 的幫助下，可能會提供全球範圍內的患者類型的廣泛覆蓋，我可以猜測、整理、翻譯、綜合，無論您想如何將其描述為您可能會看到的結果TFF 沃里？

Why don't you go ahead Zamaneh and take that one too.

為什麼不去紮馬內赫，把那個也拿走呢？

Sure. Yes. We believe that the information we gather through the expanded access program will add to the knowledge base that we're going to have about TFF VORI and it's potential. We are developing TFF VORI by conducting a clinical trial and the results of the clinical trial will lead us and help us and guide us to understand our next steps and the design of our Phase III, et cetera. but the information we're gathering through the expanded access program is very valuable and adds to that.

當然。是的。我們相信，透過擴展訪問計劃收集的資訊將豐富我們關於 TFF VORI 及其潛力的知識庫。我們正在透過進行臨床試驗來開發TFF VORI，臨床試驗的結果將引導我們、幫助我們並指導我們了解我們的下一步以及我們的III期設計等等。但我們透過擴大訪問計劃收集的資訊非常有價值，並且會增加這一點。

It also really expands the indications that we're in. The clinical trial is in invasive pulmonary aspergillosis, the expanded access program gives the opportunity for TFF VORI to be in 5 additional indications, which is really significant. So that information is really helpful to us also to understand where are the signals of efficacy where we should be pursuing further clinical trials for TFF VORI.

它也確實擴展了我們的適應症。臨床試驗針對的是侵襲性肺麴菌病，擴大的准入計畫使 TFF VORI 有機會適應另外 5 個適應症，這非常重要。因此，這些資訊對我們確實有幫助，也有助於我們了解療效訊號在哪裡，我們應該對 TFF VORI 進行進一步的臨床試驗。

I just wanted to -- I'm sorry, I just mentioned that you brought up Durbin. And one of the reasons for us signing on with Durbin is that it -- we have -- although it's not a formal clinical trial protocol, we do have a data collection mechanism that would provide us with uniformity across the various patients that come into the compassionate use program. So it's not with the same degree of rigor, but there is a systematic data collection that's planned that will allow us to characterize the patients and the outcomes. Zamaneh, I don't know if you want to add anything.

我只是想——抱歉，我剛剛提到你撫養了德賓。我們與杜賓簽約的原因之一是，儘管這不是正式的臨床試驗方案，但我們確實有一個數據收集機制，可以為我們提供進入臨床試驗的各種患者的一致性。同情使用計劃。因此，它的嚴格程度不一樣，但計劃進行系統性的資料收集，這將使我們能夠描述患者的特徵和結果。 Zamaneh，我不知道你是否想補充什麼。

Terrific, that's exactly what I was looking for. Yes, terrific. That's exactly what I was looking for. And then secondarily, I know you have cash, as Kirk said, through perhaps third quarter 2024. My model makes it easy to see that is certainly true. But if you had additional cash, what other molecules do you think you might think about advancing into clinic and make good sense in whether they be small studies or just even proof-of-concept studies where you could generate results that would be -- would provide additional opportunities for our partnerships.

太棒了，這正是我一直在尋找的。是的，太棒了。這正是我一直在尋找的。其次，正如柯克所說，也許到 2024 年第三季你都有現金。我的模型很容易看出這確實是真的。但是，如果你有額外的現金，你認為你可能會考慮哪些其他分子進入臨床，並且無論它們是小型研究還是只是概念驗證研究，你都可以產生這樣的結果，這些研究是有意義的為我們的合作夥伴關係提供更多機會。

Yes. Thank you for the question. Just to clarify, it's enough cash to get us through the first quarter of next year. And clearly, we're going to have to raise money again based on the expected inflection point from us producing data, we think will be a catalyst to allow us to raise more money. The first order of business when we raise money is to be able to continue to fund the development of TFF VORI and TFF TAC. I want to ensure that we don't drop the ball on those 2 programs and get too unfocused. So that's our initial focus.

是的。感謝你的提問。需要澄清的是，這些現金足以讓我們度過明年第一季。顯然，我們將不得不根據我們產生的數據的預期轉折點再次籌集資金，我們認為這將成為我們籌集更多資金的催化劑。當我們籌集資金時，首要任務是能夠繼續資助 TFF VORI 和 TFF TAC 的發展。我想確保我們不會在這兩個項目上犯錯，也不會太分散。這就是我們最初的重點。

But as you pointed out, there are other molecules. And we have a process underway to evaluate potential pipeline products. We've recently reacquired full rights in Niclosamide. I'm not saying we would go forward with that, but it's in -- we have it and we are currently evaluating whether it makes sense to go forward with Niclosamide and indications besides COVID-19, which was the original idea of it. And we'll evaluate that. But we also have shown that our technology is able to take, for example, a large variety of biologics like monoclonal antibodies, vaccines, we have the agreement with the NIH to develop a universal fluctuations vaccine, and mRNAs, even in bacteriophages.

但正如你所指出的，還有其他分子。我們正在評估潛在的管道產品。我們最近重新獲得了氯硝柳胺的全部權利。我並不是說我們會繼續這樣做，但我們已經有了它，我們目前正在評估繼續使用氯硝柳胺和 COVID-19 以外的適應症是否有意義，這是它的最初想法。我們將對此進行評估。但我們也已經證明，我們的技術能夠應用多種生物製品，例如單株抗體、疫苗，我們與 NIH 達成協議，開發通用波動疫苗和 mRNA，甚至是噬菌體。

And so there's -- we have a wealth of different opportunities. The key is going to be to see what we should focus on, and it's premature for me to say that with any degree of certainty, we really have to go through that evaluation process, which we will get underway and we have underway right now.

因此，我們擁有大量不同的機會。關鍵是看看我們應該關注什麼，我現在就說，無論有多少確定性，我們都必須經歷這個評估過程還為時過早，我們將開始並且現在已經開始。

The last question comes from Daniel Carlson at Tailwinds.

最後一個問題來自 Tailwinds 的 Daniel Carlson。

Just a couple of follow-up questions. Regarding the expanded access program, is that data that something you can submit to the regulatory authorities like the FDA or EMA? And will they consider that data when advising on potential next steps?

只是幾個後續問題。關於擴大訪問計劃，您可以將這些數據提交給 FDA 或 EMA 等監管機構嗎？他們在就潛在的後續步驟提供建議時會考慮這些數據嗎？

Yes. Dan, thank you for participating. I appreciate the question. We believe the answer is yes, but let me let Zamaneh elaborate.

是的。丹，謝謝你的參與。我很欣賞這個問題。我們相信答案是肯定的，但讓我讓 Zamaneh 詳細說明。

Dan, yes. Yes, we believe that will be part of the data package. The expanded access data after all is valuable and helpful data about what TFF VORI has been able to do. And the FDA does accept that as part of the data package that one submits.

丹，是的。是的，我們相信這將成為資料包的一部分。畢竟，擴展的存取數據對於 TFF VORI 的能力而言是有價值且有用的數據。 FDA 確實接受這一點作為提交的資料包的一部分。

Great. Zamaneh, you mentioned for the Phase II VORI, expanding the eligibility criteria with additional real-world criteria. Can you just elaborate on what that means exactly?

偉大的。 Zamaneh，您提到第二階段 VORI，透過額外的現實標準擴展了資格標準。能詳細說明一下這到底意味著什麼嗎？

Sure. So with every clinical trial, obviously, you need to make sure that you get the right patients, because, for example, if the patient doesn't have, let's say, aspergillosis, which responds to voriconazole, then obviously, one couldn't expect TFF VORI to cause improvement. So it's important to make sure that you get the right patients in. The diagnostic criteria that's part of the protocol that is customarily part of the protocol for IPA type studies is a very strict and academic type of diagnostic criteria, which is very valuable. But it is very strict. For example, it includes that the patients have to have certain signs and symptoms to be part of that to be eligible as part of meeting the criteria and those signs and symptoms don't include worsening cough.

當然。因此，顯然，在每項臨床試驗中，您都需要確保找到合適的患者，因為，例如，如果患者沒有曲霉病，而曲霉病對伏立康唑有反應，那麼顯然，就不可能期待TFF VORI 帶來改善。因此，確保招募到正確的患者非常重要。診斷標準是協議的一部分，通常是 IPA 類型研究協議的一部分，是一種非常嚴格和學術性的診斷標準，非常有價值。但它非常嚴格。例如，它包括患者必須具有某些體徵和症狀才有資格符合標準，並且這些體徵和症狀不包括咳嗽惡化。

Now in reality, when physicians face, for example, we're talking about the patients with hematologic malignancy. You have that patient with AML, who has now developed a fungal -- pulmonary fungal infection. They see that the patient has increased respiratory symptoms, including a productive cough that has worsened and the test CT shows a cavity and they grow aspergillus from their lungs. That patient in the real world gets treated with voriconazole for the probable diagnosis of IPA. But based on that academic set of criteria, that patient wouldn't be considered because worsening cough is not one of the specific signs and symptoms mentioned in that diagnostic criteria.

現在，在現實中，例如，當醫生面對時，我們談論的是患有血液惡性腫瘤的患者。那位 AML 患者現在患有真菌—肺部真菌感染。他們發現患者呼吸道症狀加重，包括咳嗽加劇，CT 檢測顯示有空洞，肺部長出曲霉菌。現實世界中的該患者因可能診斷為 IPA 而接受伏立康唑治療。但根據這套學術標準，該患者不會被考慮，因為咳嗽惡化並不是該診斷標準中提到的具體徵兆和症狀之一。

So after talking with our investigators, one of the -- they gave us feedback about various aspects. And one of the pieces of feedback we received was this that in the real world, we actually diagnose patients with IPA, bringing clinical judgment and putting the various parameters together to get a story, get a picture of does this fit IPA or not. And as a result of that, we have brought that into the protocol, allowing these real-world criteria like worsening cough to qualify the patient as long as other elements are met the way they're supposed to be met.

因此，在與我們的調查人員交談後，其中一位調查人員向我們提供了有關各個方面的回饋。我們收到的回饋之一是，在現實世界中，我們實際上診斷了 IPA 患者，結合臨床判斷並將各種參數放在一起來形成一個故事，以了解這是否適合 IPA。因此，我們將其納入協議中，只要其他要素按照預期的方式得到滿足，就允許咳嗽惡化等現實世界的標準使患者符合資格。

Got you. Got you. And so can you just -- can you comment at all about your screening failure rate? And will this change that?

明白你了。明白你了。那麼您能否對您的篩檢失敗率發表評論？這會改變這一點嗎？

It should. It should because, again, previously, some of the patients that didn't have the specific signs and symptoms mentioned in the algorithm, they would not qualify. And now because they've entered these real-world criteria into the protocol, they would quantify for study participation.

它應該。這應該是因為，之前，一些沒有演算法中提到的特定體徵和症狀的患者，他們不符合資格。現在，因為他們已將這些現實世界的標準輸入協議中，他們將量化研究參與。

Got you. Okay. And then one question on TAC, this be again Zamaneh that you mentioned that you're surprised how much -- how little TFF TAC, it takes to match the overall clinical outcome from oral tacrolimus. Can you elaborate on that and what that means from a clinical standpoint?

明白你了。好的。然後是關於 TAC 的一個問題，這又是 Zamaneh，您提到您很驚訝需要多少 TFF TAC 才能達到口服他克莫司的整體臨床結果。您能詳細說明一下這一點以及從臨床角度來看這意味著什麼嗎？

Yes. So patients come in, these are patients who are lung transplant recipients. They've had their lung transplant some time ago, 6 months ago or so or more, years ago. And these are patients who -- all of them are oral tacrolimus because most patients, most lung transplant recipients do go on oral tacrolimus to control rejection, and they've been on oral tacrolimus long enough to start to have the toxic effects of oral tacrolimus. So these are the patients whose kidneys are shutting down but the physician is faced with that decision of what do I do with this patient? If I continue the patient on oral tacrolimus then the dosages that I have them on, the kidneys are going to continue to worsen.

是的。所以病人進來了，這些病人是肺移植接受者。他們不久前、六個月前或更早、幾年前就進行了肺移植手術。這些患者都是口服他克莫司，因為大多數患者、大多數肺移植受者確實會服用口服他克莫司來控制排斥反應，而且他們服用口服他克莫司的時間足夠長，開始產生口服他克莫司的毒性作用。那麼，這些患者的腎臟正在關閉，但醫生面臨我該如何處理這名患者的決定？如果我繼續讓病人口服他克莫司，那麼我服用的劑量，腎臟會繼續惡化。

So I decrease the oral tacrolimus hoping they don't go into a rejection and maybe I add a different type of immunosuppressant as I decrease oral tacrolimus but that's going to have its own toxicity. So these are the types of patients right now in this study. So as we take these patients, the patients are doing well from a rejection perspective. They're not rejecting their lungs. Their oral tacrolimus is keeping rejection at bay, but their kidneys are not functioning well.

因此，我減少了口服他克莫司的用量，希望它們不會出現排斥反應，也許我在減少口服他克莫司的同時添加了另一種類型的免疫抑製劑，但這會有其自身的毒性。這些就是本研究目前的患者類型。因此，當我們收治這些患者時，從排斥的角度來看，患者表現良好。他們並沒有拒絕自己的肺。他們的口服他克莫司可以防止排斥反應，但他們的腎臟功能不佳。

So we are -- we have transitioned these patients. We've learned how to transition, have to take that dose of oral tacrolimus and understand what would be an equivalent dose in TFF TAC to keep the same blood levels. And then from there, we've learned how much can we slowly go down and see that the patients continue to be clinically stable, no clinical signs of rejections, no -- inhaled tacrolimus TFF TAC providing them with the benefits of oral tacrolimus and then starting to see the beneficial effects of lower toxicity.

所以我們——我們已經轉變了這些患者。我們已經學會如何過渡，必須服用該劑量的口服他克莫司，並了解 TFF TAC 中的等效劑量是多少才能保持相同的血液水平。然後從那裡開始，我們了解到我們可以慢慢地走下去，看到患者的臨床狀況繼續穩定，沒有排斥反應的臨床症狀，沒有吸入他克莫司TFF TAC 為他們提供口服他克莫司的好處，然後開始看到降低毒性的有益效果。

So obviously, we need to dose many more patients. That's why we think we will need approximately 10 patients to make a final call, but we're just very encouraged. TFF TAC is also the drug that when we talk with lung transplant doctors, they say this is the drug we've been waiting for. So there's a lot of enthusiasm to hopefully get this drug in the hands of patients and hopefully see how this transition helps with that improved efficacy and lower toxicity parameter. And in the long run, this is a drug that should be used in -- assuming we show the type of response we're projecting and hoping to see, this is the type of drug that should be used in patients before they develop renal toxicity.

顯然，我們需要給更多的患者服用藥物。這就是為什麼我們認為我們需要大約 10 名患者才能做出最後決定，但我們感到非常鼓舞。 TFF TAC也是當我們與肺移植醫生交談時，他們說這是我們一直在等待的藥物。因此，人們充滿熱情地希望將這種藥物送到患者手中，並希望看到這種轉變如何有助於提高療效和降低毒性參數。從長遠來看，這是一種應該使用的藥物——假設我們顯示出我們預計並希望看到的反應類型，這就是應該在患者出現腎毒性之前使用的藥物類型。

There should be no reason for us to wait for patients to develop renal toxicity from oral tacrolimus and then change them to TFF TAC. So in the long run, our goal would be to really have this available in the -- for patients from the start.

我們沒有理由等待口服他克莫司的患者出現腎毒性，然後將其改為 TFF TAC。因此，從長遠來看，我們的目標是從一開始就真正為患者提供這種服務。

Got you. That's exciting. And Zamaneh, thank you. It's obvious that you have done a lot of work at turning these programs around. So I want to thank you for your efforts in that regard -- it maybe really a broadly long way in a short time, it appears. So last question for me, Harlan. You focused rightly on the 2 Phase IIs, but there were a number of other potential balls out there in the year. I'm just wondering if there's anything progressing on the third-party work that you've been working on in the past or if that's just sort of all silent now.

明白你了。真令人興奮。還有紮馬內赫，謝謝你。顯然，您為扭轉這些計劃做了很多工作。因此，我要感謝你們在這方面所做的努力——看來，這可能是在短時間內取得的巨大進展。這是我的最後一個問題，哈倫。您正確地關注了 2 個第二階段，但這一年還有許多其他潛在的球。我只是想知道您過去一直從事的第三方工作是否有任何進展，或者現在是否只是沉默。

Thank you, Dan, for that question. We still have ongoing collaborations going with some big pharma companies and also biotech companies. It is going on in the background. The one thing we've done is we've changed the emphasis of what we're doing to throw as many hooks out there to catch fish to be more focused and go to the fishing hover where the fish actually are. And so we're saying, one, we've narrowed the focus to be only on those programs that we think we can make a real difference to our business interest, to the collaborator that might lead to -- where we can add value that might lead to a business deal in the future.

謝謝丹提出這個問題。我們仍然與一些大型製藥公司和生技公司保持著持續的合作。它正在後台發生。我們所做的一件事是，我們改變了我們正在做的事情的重點，將盡可能多的魚鉤扔到那裡去釣魚，從而更加集中註意力，並前往魚實際所在的釣魚懸停處。所以我們說，一，我們已經將重點縮小到那些我們認為可以對我們的商業利益、對合作者可能產生真正影響的項目上——我們可以在這些項目上增加價值，可能會在未來促成一項商業交易。

And the other is that we want people to pay their way completely, before we were doing quite a lot of work where we were taking on the burden of the cost. There wasn't tremendous cost, but we were taking on that burden. Now we want -- somebody wants to collaborate with us and part of demonstrating that it's important to them is for them paying their way. So we have a more narrowed group of collaborations that we have going on. And of course, we have the government collaborations, which we're very excited about. We've received that piece for our laboratory costs, our human resources devoted to those projects. And we're exploring other opportunities on the non-dilutional side of working with government and other organizations.

另一個是，在我們承擔成本負擔之前，我們希望人們完全支付自己的費用。成本不高，但我們承擔了這個負擔。現在我們想要——有人想要與我們合作，而證明這對他們很重要的一部分是讓他們付費。因此，我們正在進行的合作範圍更窄。當然，我們還有政府合作，對此我們感到非常興奮。我們已經收到了這件作品，以支付我們的實驗室費用和致力於這些專案的人力資源。我們正在探索與政府和其他組織合作的非稀釋方面的其他機會。

There no further questions. I will turn the call back over for closing comments.

沒有其他問題了。我將把電話轉回以徵求結束意見。

Well, in closing, I'd just like to thank all of you for being on today's call. And I'd especially like to thank all of our investors who've demonstrated their belief in support of our company. I'm convinced the TFF VORI and TFF TAC programs have the potential to significantly advance the current standard of care in their respective rare disease indication. And that's why I as well as our officers, directors and employees have purchased significant equity in our company. Thank you again, and we look forward to providing another corporate update in November.

最後，我想感謝大家參加今天的電話會議。我要特別感謝所有對我們公司表達支持的投資者。我相信 TFF VORI 和 TFF TAC 計劃有潛力顯著提高各自罕見疾病適應症的當前護理標準。這就是為什麼我以及我們的管理階層、董事和員工購買了我們公司的大量股權。再次感謝您，我們期待在 11 月提供另一次公司更新。

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating, and we ask that you please disconnect your lines.

女士們、先生們，今天的電話會議到此結束。我們感謝您的參與，並請您斷開線路。