Codexis Inc (CDXS) 2022 Q4 法說會逐字稿

Welcome to the Codexis Fourth Quarter and Full Year 2022 Earnings Conference Call. A question-and-answer session will follow the formal presentation. (Operator Instruction] And now I'll turn the call over to Brendan Strong from Argo Partners. Please go ahead. Thank you, operator. With me today are Dr. Stephen Dilly, Codexis President and Chief Executive Officer; Kevin Norrett, Chief Operating Officer; and Sri Ryali, Chief Financial Officer. During this call, management will be making a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including our guidance for 2023 revenue, product revenues and gross margin on product revenues as well as our strategies and prospects for revenue growth and successful execution of current and future programs and partnerships.

歡迎參加 Codexis 第四季度和 2022 年全年收益電話會議。問答環節將在正式介紹之後進行。 （接線員說明）現在我將把電話轉給 Argo Partners 的 Brendan Strong。請繼續。謝謝接線員。今天和我在一起的有 Codexis 總裁兼首席執行官 Stephen Dilly 博士；首席運營官 Kevin Norrett官員；和首席財務官 Sri Ryali。在這次電話會議中，管理層將根據 1995 年《私人證券訴訟改革法案》做出一些前瞻性陳述，包括我們對 2023 年收入、產品收入和毛利率的指導關於產品收入以及我們的收入增長戰略和前景以及當前和未來計劃和合作夥伴關係的成功執行。

To the extent that statements contained in this call are not descriptions of historical facts regarding Codexis, they are forward-looking statements reflecting the beliefs and expectations of management as of the statement date, February 23, 2023. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties and other factors that are, in some cases, beyond Codexis' control and could materially affect actual results. Additional information about factors that could materially affect actual results can be found in Codexis' filings with the Securities and Exchange Commission. Codexis expressly disclaims any intent or obligation to update these forward-looking statements, except as required by law. I'll now turn the call over to Stephen.

如果本次電話會議中包含的陳述不是對有關 Codexis 的歷史事實的描述，它們是前瞻性陳述，反映截至聲明日期 2023 年 2 月 23 日管理層的信念和期望。您不應過分依賴這些前瞻性陳述，因為它們涉及已知和未知的風險、不確定性和其他因素，在某些情況下，這些因素超出了 Codexis 的控制範圍，並可能對實際結果產生重大影響。有關可能對實際結果產生重大影響的因素的更多信息，請參閱 Codexis 向美國證券交易委員會提交的文件。 Codexis 明確否認任何更新這些前瞻性陳述的意圖或義務，除非法律要求。我現在將電話轉給斯蒂芬。

Thank you, Brendan, and thanks, everyone, for joining. As we laid out in the fourth quarter of last year, we continue to focus on prioritizing programs where Codexis has a clear competitive advantage, and we're pleased with our recent momentum. The financial results that we delivered in the fourth quarter were exactly on target and we ended 2022 with $114 million in cash, providing us with runway through the end of 2024 and giving us plenty of time to demonstrate that our new focus strategy is working. A significant activity during the second half of 2022 and early 2023 has been adding to the strength of our leadership bench. This has been happening across our executive leadership team and Board and in less visible ways throughout the organization. We've achieved this while reducing overall headcount since November.

謝謝 Brendan，也謝謝大家的加入。正如我們在去年第四季度製定的那樣，我們將繼續專注於優先考慮 Codexis 具有明顯競爭優勢的項目，我們對我們最近的勢頭感到滿意。我們在第四季度交付的財務業績完全符合目標，到 2022 年底我們擁有 1.14 億美元的現金，為我們提供了到 2024 年底的跑道，並給了我們足夠的時間來證明我們的新重點戰略正在發揮作用。 2022 年下半年和 2023 年初的一項重要活動增強了我們領導層的實力。這已經在我們的執行領導團隊和董事會中發生，並且在整個組織中以不太明顯的方式發生。自去年 11 月以來，我們在裁員的同時實現了這一目標。

To quickly recap the changes outlined in Slide 3. We Kevin Norrett, Chief Operating Officer; and Meg Fitzgerald, Chief Legal Officer and General Counsel, both joined us last fall. More recently, Sri Ryali joined us as Chief Financial Officer in January. Sri has a strong background of leading financial organizations within biopharmaceutical companies and his commercial expertise has further strengthened the breadth of our team's collective experience. We've also added new capabilities in FP&A, commercial assessment and in our translational team. Importantly, this is also happening on our Board with the recent additions of Rahul Singhvi and Stewart Parker, both bringing demonstrated track records of success in leading pharmaceutical and genomic therapy companies.

快速回顧幻燈片 3 中概述的變化。我們是首席運營官 Kevin Norrett；和首席法律官兼總法律顧問 Meg Fitzgerald 於去年秋天加入了我們。最近，Sri Ryali 於 1 月加入我們，擔任首席財務官。 Sri 擁有領先生物製藥公司金融機構的深厚背景，他的商業專長進一步加強了我們團隊集體經驗的廣度。我們還在 FP&A、商業評估和我們的翻譯團隊中增加了新功能。重要的是，這也發生在我們的董事會上，最近增加了 Rahul Singhvi 和 Stewart Parker，他們都在領先的製藥和基因組治療公司取得了成功。

Our core strength of engineering unique purpose-built enzymes for use across a range of target markets remains central to our business. However, in line with the strategy we outlined during last quarter's call, we've been deliberate about selectively deploying our platform where we see the most potential for value creation. To that end, I want to take a moment to break down the structure of our business and highlight what we view as the most promising avenues outlined here in Slide 4. In pharmaceutical manufacturing, we provide a single often bespoke enzyme engineered with specific characteristics for a specific customer. This process is relatively inexpensive given the investments we've made in CodeEvolver, but the potential annual revenue per deal is also limited, averaging about $3 million to $7 million per successful enzyme.

我們設計用於一系列目標市場的獨特專用酶的核心優勢仍然是我們業務的核心。然而，根據我們在上個季度的電話會議中概述的戰略，我們一直在慎重考慮有選擇地在我們認為最有潛力創造價值的地方部署我們的平台。為此，我想花點時間分解一下我們的業務結構，並強調我們認為最有前途的途徑，請參見幻燈片 4。在製藥業中，我們提供一種通常定制的酶，其具有特定的特性，可用於一個特定的客戶。考慮到我們在 CodeEvolver 上的投資，這個過程相對便宜，但每筆交易的潛在年收入也有限，平均每個成功的酶約 300 萬至 700 萬美元。

As you may imagine, it takes an awful lot of these to get to $1 billion revenue opportunity or even a few hundred million. As we've said before, we'll continue to invest modestly in this business, ensuring that it grows steadily and remains profitable, providing us with capital to invest in our high-priority focus areas. One of those high-priority areas is life sciences, which we view as a fruitful space for Codexis. On the genomics side, we optimize our enzymes for better performance with higher sensitivity and specificity than the existing enzymes and with an eye on making our enzymes slot easily into existing customer workflows. If we do our job well, we make it straightforward for potential customers to use Codexis enzyme and key players in the industry are taking notice. This process can be time-consuming and labor-intensive. But when we get it right, we believe the revenue opportunity is closer to $10 million to $30 million for enzyme because one enzyme can serve multiple customers.

正如您所想像的那樣，要獲得 10 億美元甚至幾億美元的收入機會，需要大量的這些。正如我們之前所說，我們將繼續對該業務進行適度投資，確保其穩步增長並保持盈利，為我們提供資金以投資於我們高度優先的重點領域。其中一個高度優先的領域是生命科學，我們認為這是 Codexis 富有成果的領域。在基因組學方面，我們優化我們的酶以獲得比現有酶更好的性能、更高的靈敏度和特異性，並著眼於使我們的酶更容易融入現有客戶的工作流程。如果我們做好我們的工作，我們會讓潛在客戶直接使用 Codexis 酶，並且行業的主要參與者會注意到這一點。這個過程可能既費時又費力。但如果我們做對了，我們相信酶的收入機會接近 1000 萬到 3000 萬美元，因為一種酶可以為多個客戶服務。

As you can see, this is 3 or 4x larger than a pharmaceutical manufacturing opportunity and well worth the extra effort. We're focused on driving our product revenues in this area over the next few years. Kevin will provide some specific examples in a few moments. We're excited about genomics and the economics are much better than in pharmaceutical manufacturing, but let's face it, we're still basically selling enzymes for a markup. We believe there are even better opportunities for us to pursue that allow us to capture more of the true value of our offering. That brings me to RNA and DNA synthesis where we can engineer enzymes to support the development of nucleic acid-based therapeutics. Our goal, particularly in RNA, is to put together suites of enzymes with unique capabilities where the same combination can have broad utility across many customers. Because the same group of enzymes be used repeatedly across diverse applications, this strategy creates potential returns that our orders of magnitude greater than our other offerings. We believe a suite of enzymes like this can be worth hundreds of millions of dollars in revenue opportunity.

如您所見，這比製藥商機會大 3 或 4 倍，非常值得付出額外的努力。未來幾年，我們將專注於推動我們在該領域的產品收入。稍後，凱文將提供一些具體示例。我們對基因組學感到興奮，而且經濟性比製藥業要好得多，但讓我們面對現實吧，我們基本上仍在銷售酶以加價。我們相信，我們有更好的機會去追求，讓我們獲得更多我們產品的真正價值。這讓我想到了 RNA 和 DNA 合成，我們可以在其中設計酶來支持基於核酸的療法的開發。我們的目標，尤其是在 RNA 領域，是將具有獨特功能的酶套件放在一起，使相同的組合可以在許多客戶中具有廣泛的實用性。由於同一組酶可在不同應用中重複使用，因此該策略創造的潛在回報比我們的其他產品高出幾個數量級。我們相信像這樣的一套酶可以帶來價值數億美元的收入機會。

Finally, our biotherapeutics business is where our technology really has the promise to create tremendous value. As shown on Slide 5, today, we are advancing a pipeline of oral enzymes and gene therapies, many of which we are working on in collaboration with Nestle Health Sciences and Takeda. Most of our near-term milestones are related to these programs. And as you'll hear today, they're moving along quite nicely. If we're successful, we have multiple shots on goal to address billion-dollar market opportunities. The first is CDX-7108, a drug candidate for the treatment of lipase deficiency in patients with exocrine pancreatic insufficiency, or EPI, a debilitating condition of the GI tract caused by conditions of impaired pancreatic function.

最後，我們的生物治療業務是我們的技術真正有望創造巨大價值的地方。如幻燈片 5 所示，今天，我們正在推進一系列口服酶和基因療法，其中許多是我們與 Nestle Health Sciences 和 Takeda 合作開發的。我們的大部分近期里程碑都與這些計劃有關。正如您今天會聽到的那樣，他們進展順利。如果我們成功了，我們將有多個目標來抓住數十億美元的市場機會。第一個是 CDX-7108，一種治療胰腺外分泌功能不全（EPI）患者脂肪酶缺乏症的候選藥物，EPI 是一種由胰腺功能受損引起的胃腸道衰弱狀況。

Let's discuss the biology briefly. Under normal conditions, pancreatic enzymes, which are important in the digestion of fat, protein and sugar are secreted directly into the duodenum through the pancreatic duct. -- exocrine pancreatic insufficiency occurs when either the pancreatic duct is blocked or the pancreas itself is damaged and insufficient enzymes reached small intestine. This leads to a wide range of problems, including weight loss, fatigue, anemia, abdominal pain and so on. The currently established treatment paradigm, pancreatic enzyme replacement therapy or PERT is based on oral administration of porcine-derived pancreatic enzymes.

讓我們簡單地討論一下生物學。在正常情況下，對脂肪、蛋白質和糖的消化很重要的胰酶通過胰管直接分泌到十二指腸。 -- 當胰管被阻塞或胰腺本身受損並且到達小腸的酶不足時，就會發生胰腺外分泌功能不全。這導致了範圍廣泛的問題，包括體重減輕、疲勞、貧血、腹痛等。目前建立的治療範例、胰酶替代療法或 PERT 是基於口服豬源性胰酶。

There are 3 main issues with this approach. Firstly, the practicalities of harvesting sufficient porcine enzymes to address the market is daunting. Secondly, the enzymes are given orally, so they had to pass through the various CITIC environment in the stomach before reaching the small intestine wheat is absorbed. Finally, the dosing regimen tends to be onerous with patients requiring multiple doses per meal to achieve adequate lipase levels of (inaudible). Despite these challenges, the 2 leading products on the market today have combined annual sales of greater than $1.5 billion. CDX-7108 has the potential to address all 3 of these limitations of current PERT therapy as shown on Slide 6. Firstly, CDX-7108 is a recombinant protein produced in e coli, so production is easily scalable. Secondly, CDX-7108 has been engineered to be stable even in various civic conditions that can transit through the stomach without losing activity. Thirdly, CDX-7108 is sufficiently potent as a IPACE to potentially support treatment with a single capture per meal. We believe this trifecta of manufacturability, durability and potency can translate into a very exciting commercial potential.

這種方法有 3 個主要問題。首先，收穫足夠的豬酶以滿足市場需求的可行性令人望而生畏。其次，酵素是口服的，所以要經過胃裡的各種中信環境，才能到達小腸小麥被吸收。最後，給藥方案往往繁瑣，患者每餐需要多次給藥才能達到足夠的脂肪酶水平（聽不清）。儘管存在這些挑戰，當今市場上的 2 種領先產品的年銷售額總和超過 15 億美元。 CDX-7108 有潛力解決當前 PERT 療法的所有 3 個局限性，如幻燈片 6 所示。首先，CDX-7108 是一種在大腸桿菌中產生的重組蛋白，因此生產很容易擴展。其次，CDX-7108 經過精心設計，即使在各種城市條件下也能保持穩定，可以通過胃而不會失去活性。第三，CDX-7108 作為 IPACE 具有足夠的效力，可以支持每餐一次捕獲的治療。我們相信可製造性、耐用性和效力的三重奏可以轉化為非常令人興奮的商業潛力。

Moving to Slide 7. That's why we were so excited to recently review our first clinical data from 48 normal volunteers and 5 patients with EPI treated with CDX-7108. Importantly, the safety profile was quite reassuring with no significant adverse events attributed to treatment. In the patients, we measured fat absorption following CDX-7108 or placebo in a crossover design using the 13 C02 label breath test. INBRACE, patients either fatty meal labeled with a (inaudible) carbon 13 in the fat and then we measure the above of carbon 13 exhaled over the next 4 hours. The results were exactly as we'd hoped, showing increased fat absorption in the CDX-7108 arm and a very encouraging potency and duration of action. Beside to say, we and our colleagues at Nestle are very encouraged by what we've seen and decided to move forward expeditiously with a Phase II trial that we expect to initiate in early 2024.

轉到幻燈片 7。這就是為什麼我們最近如此興奮地回顧了來自 48 名正常志願者和 5 名接受 CDX-7108 治療的 EPI 患者的第一份臨床數據。重要的是，安全性非常令人放心，沒有因治療引起的重大不良事件。在患者中，我們使用 13 C02 標籤呼氣試驗在交叉設計中測量了 CDX-7108 或安慰劑後的脂肪吸收。 INBRACE，患者在脂肪中標有（聽不清）碳 13 的脂肪餐，然後我們測量在接下來的 4 小時內呼出的碳 13 以上。結果正如我們所希望的那樣，顯示出 CDX-7108 手臂的脂肪吸收增加以及非常令人鼓舞的效力和作用持續時間。除此之外，我們和雀巢的同事對我們所看到的情況感到非常鼓舞，並決定迅速推進我們預計在 2024 年初啟動的 II 期試驗。

Similarly, as outlined on Slide 8, we are excited about our collaboration with Takeda with our gene therapy programs continuing to track towards the goals we outlined a few months ago. Here, we're using CodeEvolver to engineer proteins that may improve targeting and expression within the body when administered as transgenes and gene therapies, potentially offering improved therapeutic benefit as compared with current treatment options across a range of rare genetic disorders. As you may have seen yesterday, we highlighted preclinical data from the Fabry disease transgene program that Takeda will soon be presenting at the 19th Annual World Symposium. Fabry disease is a rare lysosomal storage disorder in which the body cannot efficiently break down lipid into smaller components and the enzyme replacement therapies currently available for treatment are compromised by their short in vivo half-life and the development of antidrug antibodies. As part of our work with Takeda, we engineered a protein variant with enhanced stability and potentially reduced immunogenicity to try to overcome these limitations.

同樣，如幻燈片 8 所述，我們對與武田的合作感到興奮，我們的基因治療計劃將繼續追踪我們幾個月前概述的目標。在這裡，我們使用 CodeEvolver 來設計蛋白質，當作為轉基因和基因療法施用時，這些蛋白質可能會改善體內的靶向和表達，與目前針對一系列罕見遺傳疾病的治療方案相比，可能會提供更好的治療效果。正如您昨天可能看到的那樣，我們重點介紹了武田即將在第 19 屆年度世界研討會上展示的法布里病轉基因項目的臨床前數據。法布里病是一種罕見的溶酶體貯積症，身體無法有效地將脂質分解成更小的成分，目前可用於治療的酶替代療法因其體內半衰期短和抗藥抗體的發展而受到損害。作為我們與武田合作的一部分，我們設計了一種具有增強穩定性和可能降低免疫原性的蛋白質變體，以試圖克服這些限制。

While this update is encouraging in isolation, this strategic partnership has also allowed us to demonstrate the power of our CodeEvolver enzyme engineering platform in the context of gene therapy more broadly. Our ability to tailor enzymes with precise and desirable characteristics makes us an incredibly powerful collaborator. And this program is indicative of how we can leverage our transgene engineering capabilities to introduce new and potentially more efficacious therapeutic options for rare diseases where the unmet need remains high. We understand that the IND preparation work within full swing, which logically leads to the entry into patients around the turn of this year.

雖然這一更新單獨來看是令人鼓舞的，但這種戰略合作夥伴關係也讓我們能夠更廣泛地展示我們的 CodeEvolver 酶工程平台在基因治療背景下的強大功能。我們定制具有精確和理想特性的酶的能力使我們成為一個非常強大的合作者。這個項目表明我們可以如何利用我們的轉基因工程能力為未滿足需求仍然很高的罕見疾病引入新的和可能更有效的治療選擇。據我們了解，IND 準備工作正在如火如荼地進行，這順理成章地導致在今年年初左右進入患者。

To sum it up, with a strong team in place and a rich set of upcoming catalysts, the next 18 months will be a critical period for Codexis. As demonstrated by the updates I've shared, our strategy is all about clear prioritization and steady execution, focusing on programs that can create the most potential value. Now I'd like to hand the call over to Kevin to dive further into our commercial strategy across each market...

總而言之，憑藉一支強大的團隊和一系列即將到來的催化劑，未來 18 個月將是 Codexis 的關鍵時期。正如我分享的更新所表明的那樣，我們的戰略就是明確的優先次序和穩定的執行，專注於能夠創造最大潛在價值的項目。現在我想把電話轉給凱文，讓他進一步深入研究我們在每個市場的商業戰略……

Thank you, Stephen. Moving to Slide 9. We have continued to modestly invest in our pharmaceutical manufacturing focus area to build a pipeline of Phase II and earlier clinical programs, which should ensure continued growth into the latter part of the decade. However, these opportunities are customized one-on-one projects with some taking 5-plus years to market. When we look at our life sciences focus area, we have developed a pipeline of enzymes to address many challenges across multiple customers, outlined on Slide 10. We have designed our enzymes to be more sensitive, more robust and more optimized to easily drop into existing workflows. A good example is our newly engineered DNA ligate for next-generation sequencing or NGS. Ligase enzymes are used to barcode the pieces of DNA in a sample so they can be read on a sequencer, making them critical to detecting a signal. Natural ligases have a ligation efficiency of approximately 40% to 50%, meaning that about 50% to 60% of any DNA sample goes on barcode and therefore, is not sequenced or detect.

謝謝你，斯蒂芬。轉到幻燈片 9。我們繼續適度投資於我們的製藥重點領域，以建立 II 期和早期臨床項目的管道，這將確保在本十年後半期持續增長。然而，這些機會是定制的一對一項目，有些需要 5 年以上的時間才能上市。當我們審視我們的生命科學重點領域時，我們已經開發出一系列酶來解決多個客戶面臨的許多挑戰，如幻燈片 10 所示。我們將酶設計得更靈敏、更穩健和更優化，以便輕鬆融入現有工作流程。一個很好的例子是我們新設計的用於下一代測序或 NGS 的 DNA 連接物。連接酶用於對樣本中的 DNA 片段進行條形碼化，以便在測序儀上讀取它們，這使得它們對於檢測信號至關重要。天然連接酶的連接效率約為 40% 至 50%，這意味著任何 DNA 樣本中約有 50% 至 60% 都帶有條形碼，因此未被測序或檢測。

In comparison, our newly engineered DNA ligase achieves over 90% ligation efficiency. This is a significant improvement when you are searching for a needle in a haystack across small tissue sets. Not only is this ligase more sensitive and efficient, but it was developed using common test kits and buffers, but it is an easy drop-in solution across multiple customer workflows. Earlier this month, I had the opportunity to discuss our preliminary data from our DNA ligase white paper with many potential customers at the Advances in Genome Biology and Technology Conference, or AGBT. There was a lot of interest in this enzyme from multiple large NGS players, and we plan to deliver the research-grade version to customers for testing in the second quarter. We also will have commercial supply available later this year.

相比之下，我們新設計的 DNA 連接酶可達到 90% 以上的連接效率。當您在小型組織組中大海撈針時，這是一項重大改進。這種連接酶不僅更加靈敏和高效，而且它是使用通用測試套件和緩衝液開發的，而且它是跨多個客戶工作流程的簡單插入式解決方案。本月早些時候，我有機會在基因組生物學和技術進展會議 (AGBT) 上與許多潛在客戶討論了我們 DNA 連接酶白皮書中的初步數據。多家大型 NGS 廠商對這種酶很感興趣，我們計劃在第二季度向客戶提供研究級版本進行測試。我們還將在今年晚些時候提供商業供應。

Finally, Roche, who previously licensed a different DNA ligase from us in 2019 just exercised their right of first negotiation on this newly engineered version. As part of this, we will begin negotiating potential terms with them over the next 90 days. If you are interested in learning more about our new and engineered DNA like, a copy of the white paper is available under the Resources tab on our corporate website. In the RNA and DNA synthesis space, we can enable the development of nucleic acid-based therapeutics. For example, on Slide 11, our high CAF RNA polymerase is the first enzyme we engineered to support mRNA synthesis. This enzyme increases capping efficiency and significantly decreases the unwanted byproduct of double-stranded RNA. We launched this enzyme in late 2020 21 and continue to gain customer traction with multiple RNA manufacturers. This enzyme was our entry point into mRNA manufacturing, and we are now developing a suite of enzymes to support these customers. Looking ahead, we expect to launch at least one other enzyme in this arena before the end of the even previously mentioned that the same group of enzymes can be used repeatedly across diverse applications, allowing for our strategy to drive potential returns that are orders of magnitude greater than our other offerings.

最後，之前在 2019 年從我們這裡獲得了另一種 DNA 連接酶許可的羅氏公司剛剛行使了他們對這個新設計版本的優先談判權。作為其中的一部分，我們將在接下來的 90 天內開始與他們協商潛在條款。如果您有興趣了解更多關於我們新的和工程化的 DNA，例如，可以在我們公司網站的“資源”選項卡下獲取白皮書的副本。在 RNA 和 DNA 合成領域，我們可以開發基於核酸的療法。例如，在幻燈片 11 中，我們的高 CAF RNA 聚合酶是我們設計的第一種支持 mRNA 合成的酶。這種酶提高了加帽效率並顯著減少了雙鏈 RNA 的不需要的副產物。我們於 2020 年底推出了這種酶21，並繼續吸引多家 RNA 製造商的客戶。這種酶是我們進入 mRNA 製造的切入點，我們現在正在開發一套酶來支持這些客戶。展望未來，我們希望在之前提到的同一組酶可以在不同應用中重複使用，從而使我們的戰略能夠推動數量級的潛在回報之前，在這個領域推出至少一種其他酶大於我們的其他產品。

On Slide 12, in oligonucleotide senses, our engineered TDT polymerase is a perfect example. We have developed this enzyme for our partner, molecular assemblies to enable more efficient and customized DNA synthesis. The TDT polymerase adds any 1 of 4 DNA-based units onto the end of a growing chain regardless of the prior sequence of that chain and then stops before the next program step occurs and the next base unit is added. This enables DNA sequences to be built to order in a controlled fashion. Moving to Slide 13. We are now applying the same approach to RNA synthesis. Over the last year, we have been focused on developing a suite of enzymes to support short interference RNA or siRNA manufacturing. Over 300 RNAi therapies are currently in development, and we want to be positioned to help any one of these companies manufacture commercial level supply of their RNA therapeutics.

在幻燈片 12 上，在寡核苷酸意義上，我們的工程 TDT 聚合酶是一個完美的例子。我們為我們的合作夥伴分子組裝開發了這種酶，以實現更高效和定制的 DNA 合成。 TDT 聚合酶將 4 個基於 DNA 的單元中的任意一個添加到增長鏈的末端，而不管該鏈的先前序列如何，然後在下一個程序步驟發生和添加下一個鹼基單元之前停止。這使得 DNA 序列能夠以受控方式按順序構建。轉到幻燈片 13。我們現在將相同的方法應用於 RNA 合成。在過去的一年裡，我們一直專注於開發一套酶來支持短干擾 RNA 或 siRNA 的生產。目前有超過 300 種 RNAi 療法正在開發中，我們希望能夠幫助這些公司中的任何一家製造其 RNA 療法的商業級供應。

Today, biopharmaceutical companies use phosphoramidite chemistry to develop small quantities of siRNA. This process is expensive and creates a lot of chemical ways. Assuming these companies receive FDA approval for their therapies, they will need new solutions to efficiently scale up manufacturing to large qualities. We believe we are close to an enzymatic solution that can lower costs and same time, and we plan to share more information on the technology platform at the Ties media. Wrapping up Life Sciences, our goal is to develop differentiated enzymes that solve complex problems for multiple customers. First, with plug-and-play solutions in genomics and NGS second with a suite of enzymes and methods in RNA and DNA synthesis to support the development of nucleic acid-based therapeutics. Finally, I'd like to take a moment to revisit the enhanced commercial focus we discussed on our last call, outlined on Slide 14.

今天，生物製藥公司使用亞磷酰胺化學來開發少量的 siRNA。這個過程很昂貴，並且會產生很多化學方法。假設這些公司的療法獲得 FDA 批准，他們將需要新的解決方案來有效地擴大生產規模以達到高質量。我們相信我們已經接近於能夠同時降低成本和時間的酶促解決方案，我們計劃在 Ties 媒體上分享更多關於該技術平台的信息。總結生命科學，我們的目標是開發差異化酶，為多個客戶解決複雜問題。首先，基因組學和 NGS 中的即插即用解決方案，其次是 RNA 和 DNA 合成中的一套酶和方法，以支持基於核酸的療法的發展。最後，我想花點時間重新審視一下我們在上次電話會議上討論的增強的商業重點，幻燈片 14 對此進行了概述。

Last quarter for our Biotherapeutics pipeline, we told you that we were prioritizing assets that we have a clear understanding of the investment needed to support partnering or Codexis-driven development of our most promising clinical candidates. We are doing just that, and our collaboration with Nestle is a great example of how we can effectively leverage strong partners to derisk our programs and rapidly penetrate markets. For instance, CDX-7108, as you just heard from Stephen, this program is targeting an existing $1.5 billion. We've used the CodeEvolver platform to engineer a differentiated life space with the potential to address limitations of the standard of care treatment options in exocrine pancreatic insufficiency. Meanwhile, our partner, Nestle brings existing market presence and robust commercial infrastructure in the space. By combining the strengths of each respective organization, we are poised to deliver long-term value creation. With that, I will now turn the call over to Sri to discuss our financial results for the quarter.

上個季度，對於我們的生物治療管道，我們告訴您我們正在優先考慮資產，我們清楚地了解支持合作或 Codexis 驅動的我們最有前途的臨床候選人的開發所需的投資。我們正在這樣做，我們與雀巢的合作是一個很好的例子，說明我們如何有效地利用強大的合作夥伴來降低我們項目的風險並迅速滲透市場。例如，CDX-7108，正如您剛剛從斯蒂芬那裡聽到的那樣，該計劃的目標是現有的 15 億美元。我們使用 CodeEvolver 平台設計了一個差異化的生活空間，有可能解決胰腺外分泌功能不全的標準護理治療方案的局限性。同時，我們的合作夥伴雀巢在該領域帶來了現有的市場影響力和強大的商業基礎設施。通過結合每個組織的優勢，我們準備好創造長期價值。有了這個，我現在將把電話轉給 Sri 來討論我們本季度的財務業績。

Thank you, Kevin, and good afternoon, everyone. Let me dive into the highlights of our full year 2022 financial results, starting with Slide 15. Total revenues for fiscal year 2022 were $138.6 million, an increase of 32% from $104.8 million for the prior year. including enzyme sales related to tax loaded, which were $75.4 million and $34.5 million for 2022 and 2021, respectively. Total revenues for fiscal year 2022 were $63.2 million, a decrease of 10% from $70.3 million in the prior year. Product revenues for 2022 were $116.7 million, an increase of 65% from $70.7 million the prior year, primarily driven by enzyme sales related to tax Slovin, -- excluding these sales, total product revenues for fiscal year 2022 were $41.3 million, an increase of 14% from $36.1 million in the prior year. R&D revenues were $21.9 million for fiscal year 2022 compared to $34.1 million in the prior year. The decrease was driven by lower license fees and decreased revenue from milestone payments as well as lower R&D fees from existing collaboration agreements.

謝謝你，凱文，大家下午好。讓我從幻燈片 15 開始深入了解我們 2022 年全年財務業績的亮點。2022 財年的總收入為 1.386 億美元，比上一年的 1.048 億美元增長 32%。包括與稅收相關的酶銷售額，2022 年和 2021 年分別為 7540 萬美元和 3450 萬美元。 2022 財年的總收入為 6320 萬美元，比上年的 7030 萬美元下降 10%。 2022 年的產品收入為 1.167 億美元，比上年的 7070 萬美元增長 65%，這主要是受與稅收 Slovin 相關的酶銷售的推動——不包括這些銷售，2022 財年的產品總收入為 4130 萬美元，增長了比上一年的 3610 萬美元增長 14%。 2022 財年的研發收入為 2190 萬美元，上年為 3410 萬美元。減少的原因是較低的許可費用和里程碑付款的收入減少以及現有合作協議的較低研發費用。

Product gross margin for fiscal year 2022 was 67% compared to 69% in the prior year. The decrease was primarily driven by changes in sales mix and higher shipping costs. Turning to operating expenses. R&D expenses for fiscal year 2022 increased to $80.1 million compared to $55.9 million in the prior year. Selling, general and administrative expenses for fiscal year 2022 were $52.2 million compared to $49.3 million in the prior year. We also recognized $3.2 million in restructuring charges related to the workforce reduction plan we announced in the fourth quarter of last year. The net loss for fiscal year 2022 was $33.6 million or $0.51 per share compared to $21.3 million or $0.33 per share for fiscal year 2021. As of December 31, 2022, we had $114 million in cash and cash equivalents.

2022 財年的產品毛利率為 67%，上年為 69%。減少的主要原因是銷售組合的變化和更高的運輸成本。轉向運營費用。 2022 財年的研發費用從上一年的 5590 萬美元增加到 8010 萬美元。 2022 財年的銷售、一般和行政費用為 5220 萬美元，上年為 4930 萬美元。我們還確認了與去年第四季度宣布的裁員計劃相關的 320 萬美元重組費用。 2022 財年的淨虧損為 3360 萬美元或每股 0.51 美元，而 2021 財年為 2130 萬美元或每股 0.33 美元。截至 2022 年 12 月 31 日，我們擁有 1.14 億美元的現金和現金等價物。

In addition, we have not drawn any funds from our $50 million ATM facility we put in place in May of 2021. I'd like to spend a moment breaking down our financial results by segment, as outlined here on Slide 16. Revenue in our Performance Enzymes business increased 40% to $126.6 million in 2022. I -- before the allocation of corporate overhead expense, operating income for this segment was $46.4 million in 2022 for an operating profit margin of 39%. In our biotherapeutics business, revenue was $12 million, and we generated an operating loss of $41.2 million, again, before the allocation of corporate overhead expenses. Our operating losses in this business increased year-over-year as we grew in advance CDX-7108 as well as our self-funded programs.

此外，我們還沒有從 2021 年 5 月設立的 5000 萬美元 ATM 設施中提取任何資金。我想花點時間按部門細分我們的財務業績，如幻燈片 16 中所述。我們的收入Performance Enzymes 業務在 2022 年增長了 40%，達到 1.266 億美元。在分配公司管理費用之前，該部門 2022 年的營業收入為 4640 萬美元，營業利潤率為 39%。在我們的生物治療業務中，收入為 1200 萬美元，在分配公司管理費用之前，我們再次產生了 4120 萬美元的運營虧損。隨著我們提前發展 CDX-7108 以及我們的自籌資金計劃，我們在這項業務中的經營虧損同比增加。

Turning to guidance, as outlined on Slide 17, we expect total revenues in 2023 to be in the range of $63 million to $68 million. This range excludes revenue from enzyme sales related to Pac login and is in line with 2022 revenue. As you may recall, when we announced the amendment of our supply agreement with Pfizer last July, it included a $25.9 million retainer fee that was paid to us in 2022. We'll be recognizing this amount as noncash revenue over the course of 2023 and 2024. As we do not know the actual timing or amount that we may record in 2023, you've excluded it from our revenue guidance. If you choose to include that in your model, I would encourage you to do so in the fourth quarter. We expect product revenues to be in the range of $35 million to $40 million.

轉向指導，如幻燈片 17 所述，我們預計 2023 年的總收入將在 6300 萬至 6800 萬美元之間。該範圍不包括與 Pac 登錄相關的酶銷售收入，與 2022 年的收入一致。您可能還記得，當我們去年 7 月宣布修訂與輝瑞的供應協議時，其中包括 2022 年支付給我們的 2590 萬美元的保留費。我們將在 2023 年和2024 年。由於我們不知道我們可能在 2023 年記錄的實際時間或金額，因此您已將其排除在我們的收入指導之外。如果您選擇將其包含在您的模型中，我鼓勵您在第四季度這樣做。我們預計產品收入將在 3500 萬至 4000 萬美元之間。

As you heard from Stephen and Kevin, we expect growth from our Life Science business in 2023 to offset the year-over-year variability in the pharma manufacturing business. We expect R&D revenues to be in the range of $25 million to $30 million. Gross margin on product revenue is expected to be in the range of 68%, 73%. As Stephen noted, we expect that our existing cash and cash equivalents, combined with our future expectations for product revenues, R&D revenues and expense management will be sufficient to fund our planned operations through the end of 2024. I'll now turn the call back to Stephen.

正如您從 Stephen 和 Kevin 那裡聽到的那樣，我們預計 2023 年生命科學業務的增長將抵消製藥業務的同比變化。我們預計研發收入將在 2500 萬至 3000 萬美元之間。產品收入的毛利率預計在68%、73%之間。正如斯蒂芬指出的那樣，我們預計我們現有的現金和現金等價物，加上我們對產品收入、研發收入和費用管理的未來預期，將足以為我們到 2024 年底的計劃運營提供資金。我現在回電話斯蒂芬。

Thank you, Sri. In closing, we've delivered exactly what we promised last quarter in terms of Q4 revenues, cash position and cash runway. Our difficult strategic decisions towards the last few months of 2022 have paid off in opening up many potential avenues for revenue generation going forward. I continue to be excited about the development of the team as we equip ourselves for the next leg of a journey. Now we'd be happy to take your questions. Operator?

謝謝你，斯里。最後，我們在第四季度的收入、現金狀況和現金跑道方面完全實現了上個季度的承諾。我們在 2022 年最後幾個月做出的艱難戰略決策取得了成效，為未來的創收開闢了許多潛在途徑。我繼續對團隊的發展感到興奮，因為我們為下一段旅程做好準備。現在我們很樂意回答您的問題。操作員？

Thank you. At this time, we'll be conducting a question-and-answer session. (Operator Instruction] One moment, please, will be polled for questions. Thank you. Our first question is from the line of Steven Mah with Cowen Company.

謝謝。此時，我們將進行問答環節。 （操作員說明）請稍等，我們將對問題進行投票。謝謝。我們的第一個問題來自 Cowen 公司的 Steven Mah。

Congrats on the therapeutics progress, and welcome Shri. Can you guys hear me... Thank you. NO problem. So, a question on 7108. Can you provide some color on the initiation of the Phase II study in early 2024? Is there a reason why it can't start earlier?

祝賀治療取得進展，歡迎 Shri。你們能聽到我...謝謝。沒問題。那麼，關於 7108 的問題。您能否提供一些關於 2024 年初啟動 II 期研究的顏色？有沒有不能早點開始的原因？

The time line is principally driven by CMC considerations. We want to get the final formulation in place by the time we go into the very definitive Phase II program. And we're actively working on that right now. And we're confident that we can have everything in place for early 2024. We will obviously try and beat that if we can.

時間表主要是由 CMC 考慮因素驅動的。我們希望在我們進入非常明確的第二階段計劃時獲得最終的配方。我們現在正在積極努力。我們相信我們可以在 2024 年初準備好一切。如果可以的話，我們顯然會嘗試並擊敗它。

Okay. No, understood. And then I saw in the separate press release, you said the Phase II study is expected to take about 12 months. Is there a sense for the number of patients that are going to be in that Phase II trial? And what I'm getting at is, given that it's a fairly rare disease, will the trial be able to enroll that quickly to achieve that timing?

好的。不，明白。然後我在單獨的新聞稿中看到，您說 II 期研究預計需要大約 12 個月。是否了解將要參加該 II 期試驗的患者數量？我的意思是，考慮到這是一種相當罕見的疾病，該試驗是否能夠迅速招募到該時間點？

So yes, there's a number -- let me unpack that a little bit and say in terms of trial size in the Phase II study, the next one that we'll be initiating, we see that somewhere in the range of 40 or 50 patients. The Phase Ib, which was relatively slow to enroll, was using essentially a single site, and we're going to be going to multiple sites in multiple countries for the Phase II. We're sharpening the pencil on exactly how many right now. But given the sort of the nature of the protocol, we'd expect 15 to 20 centers to do that sort of 40 to 50 patients, which should, therefore, go a lot quicker.

所以是的，有一個數字——讓我稍微解釋一下，就 II 期研究的試驗規模而言，我們將啟動的下一個研究，我們看到大約有 40 或 50 名患者. Ib 階段的註冊速度相對較慢，基本上使用的是一個站點，我們將在第二階段前往多個國家/地區的多個站點。我們現在正在削尖鉛筆到底有多少。但考慮到協議的性質，我們預計有 15 到 20 個中心可以處理 40 到 50 名患者，因此應該會快得多。

Okay. Understood. -- for the additional color. So maybe just pivoting over to Life Science tools enzymes, specifically on the second-generation DNA ligase for Indice prep. On the Roche right of first negotiation, you mentioned they had 90 days. Does that mean that they have 90 days to come up with a deal with you guys and then that's really available to transact with other counterparties?

好的。明白了。 -- 額外的顏色。因此，也許只是轉向生命科學工具酶，特別是用於 Indice 製備的第二代 DNA 連接酶。關於羅氏的首次談判權，你提到他們有 90 天的時間。這是否意味著他們有 90 天的時間與你們達成協議，然後真的可以與其他交易對手進行交易？

Sure. Stepen, this is Kevin. Essentially, we have 90 days of good pace negotiations. If we want to continue past that, we can certainly open that discussion with them longer, but we can obviously open the discussion with other players at that time.

當然。斯蒂芬，這是凱文。從本質上講，我們有 90 天的進展順利的談判。如果我們想繼續過去，我們當然可以與他們展開更長時間的討論，但我們顯然可以在那個時候與其他玩家展開討論。

Okay. All right. Perfect. And then on the first-generation ligase that they already have license is there a status you can share with us on the status of that kit?

好的。好的。完美的。然後關於他們已經獲得許可的第一代連接酶，您是否可以與我們分享該套件的狀態？

Sure. First thing, just to clarify, this is a newly engineered DNA like as opposed to a second generation. So, it was engineered off on a different backbone just to clarify that point. And then secondly, we've been communicating with Roche over the launch of the EVOT4 DNA ligase that they licensed from us in 2019 and are expecting our first commercial sales this year, but don't have clarity exactly what quarter at this point.

當然。首先，澄清一下，這是一種新設計的 DNA，與第二代不同。因此，它是在不同的主幹上設計的，只是為了澄清這一點。其次，我們一直在與羅氏就他們在 2019 年從我們那裡獲得許可的 EVOT4 DNA 連接酶的推出進行溝通，並預計我們今年將進行首次商業銷售，但目前尚不清楚具體是哪個季度。

Okay. Understood. And then if I can sneak one last question in, and this is for you, Kevin, as well. You said you'd be tweaking the sales model and modestly increasing the sales footprint to target midsized drug manufacturers. Could you give us an update on -- is that completed or give us some timing on completion of that?

好的。明白了。然後，如果我可以偷偷提出最後一個問題，這也是給你的，凱文。你說你會調整銷售模式並適度增加銷售足跡以瞄準中型藥品製造商。您能否向我們提供有關完成的最新信息，或者給我們一些完成時間？

Sure. So just a little bit more color on that, too. Then the last 4 or 5 months has been diagnosing sort of the approach from a commercial standpoint. And what's been surprising to me is as we've been trying to grow the segment, how little we focused in terms of front-end facing sales people in terms of pull-through of enzyme sales. Now we only have 3 products on the market, but now we've looked at not only that resourcing there and looking to modestly increase it, we're still in progress of actually doing that. So, it's not complete yet. I expect that to be done probably by the end of this quarter. And that's where I think we'll start to see some increased lift in terms of our existing products and product sales increasing.

當然。所以也只是多一點顏色。然後過去 4 或 5 個月一直在從商業角度診斷某種方法。令我驚訝的是，當我們一直在努力擴大這一細分市場時，我們對面向前端的銷售人員在酶銷售方面的關注是多麼少。現在我們在市場上只有 3 種產品，但現在我們不僅研究了那裡的資源並希望適度增加它，我們仍在實際進行中。所以，它還沒有完成。我預計這可能會在本季度末完成。這就是我認為我們將開始看到我們現有產品和產品銷售增長的提升。

Our next question is coming from the line of Brandon Couillard with Jefferies.

我們的下一個問題來自 Jefferies 的 Brandon Couillard。

(inaudible) it has to be willing to kind of share the revenue base for Life Science enzymes in '22 and maybe some goal post parameters in terms of what you're expecting for growth in that portfolio in '23..

（聽不清）它必須願意在 22 年分享生命科學酶的收入基礎，並且可能根據您對 23 年該產品組合增長的預期來分享一些目標後參數。

So, we haven't disclosed a lot of information around Life Sciences as it's still relatively in its infancy. As I mentioned, Stephen, we're still sort of building the sales plan. One of the things that I just in my assessment has been -- we've been very focused on sort of customized enzyme engineering agreements over the last couple of years and a little less focused on actual customer engagement and pull-through in account planning. And that's where we're focused now. So, we expect to bring more of that information towards the end of the year. But as we're getting the plans in place, we haven't put anything forward at this point, but we definitely want to provide more color on that.

因此，我們還沒有透露很多關於生命科學的信息，因為它還處於起步階段。正如我提到的，斯蒂芬，我們仍在製定銷售計劃。我剛剛在評估中提到的一件事是——在過去的幾年裡，我們一直非常關注某種定制的酶工程協議，而不太關注實際的客戶參與和客戶規劃的推進。這就是我們現在關注的地方。因此，我們希望在年底前帶來更多此類信息。但是當我們制定計劃時，我們目前還沒有提出任何建議，但我們肯定想提供更多的顏色。

Think I would add to that... In terms of our revenue guidance. The growth that we're expecting in Life Sciences, we're expecting that to offset some of the year-over-year variability in pharma manufacturing. So when you look at our revenue guidance -- the low end of that is in line with 2022 and as Kevin indicated, the growth that we would expect it to be primarily on the Life Sciences side, and we'll have more details on that throughout this year.

我想我會補充一點……就我們的收入指導而言。我們預期生命科學領域的增長，我們預計這將抵消製藥製造業的一些同比變化。因此，當您查看我們的收入指引時——它的低端與 2022 年一致，正如凱文所指出的那樣，我們預計它的增長主要在生命科學方面，我們將提供更多詳細信息全年。

Okay. Then yesterday, Maraba announced the acquisition of Alphazyme who you partner with on at least 3 life sciences enzymes. Are there any implications of that deal as far as Codexis is concerned? Any changes in the commercial relationship? And do you own all the IP for those 3 enzymes that you've commercialized with them?

好的。昨天，Maraba 宣布收購 Alphazyme，您在至少 3 種生命科學酶方面與之合作。就 Codexis 而言，該交易是否有任何影響？商業關係有何變化？您是否擁有與他們一起商業化的那 3 種酶的所有知識產權？

So first, this is Kevin. First answer is, yes, we own all the IP with regards to those enzymes. And I just recently got back from the AGBT conference where I met with those folks was aware of some of the news coming out there and our business relationship with them is really solid. They've been good partners for us in terms of being able to execute and deliver enzymes downstream. We obviously are going to look at as we have been for some time, second sources of supply. But that being said, the business relationship is in good shape.

首先，這是凱文。第一個答案是，是的，我們擁有與這些酶有關的所有知識產權。我最近剛從 AGBT 會議回來，在那裡我會見了那些人，他們知道那里傳出的一些消息，我們與他們的業務關係非常牢固。就能夠在下游執行和遞送酶而言，他們一直是我們的好夥伴。我們顯然會像過去一段時間一樣關注第二供應來源。但話雖如此，業務關係仍處於良好狀態。

Great. And then last one for Sri. Any color you're willing to share as far as revenue pacing for the year? I know your prior CFO like to have this 40-60 kind of framework, but any color as far as just phasing?

偉大的。然後是 Sri 的最後一個。就今年的收入節奏而言，您願意分享什麼顏色？我知道你之前的 CFO 喜歡這種 40-60 的框架，但就階段性而言，有什麼顏色嗎？

You're talking about just in terms of the quarterly phasing?

您是在談論季度分階段嗎？

Yes. Our first half, second half, you do it to be aware of?

是的。我們的上半場，下半場，你做到了嗎？

Yes. So, we haven't provided quarterly revenue guidance. I think one of the things that I've observed in the month on the job here is that the pharma manufacturing revenues are inherently lumpy and it's hard to predict those quarter-to-quarter, let alone year-to-year. So, we haven't gone as far to provide quarter-over-quarter guidance yet on revenue, we're very comfortable with the full year range of the $63 million to $68 million for total revenue.

是的。因此，我們沒有提供季度收入指引。我認為我在這個月的工作中觀察到的一件事是，製藥業的收入本質上是不穩定的，很難按季度預測，更不用說按年預測了。因此，我們還沒有就收入提供季度環比指導，我們對 6300 萬美元至 6800 萬美元的全年總收入範圍感到非常滿意。

Our next question is from the line of -- Do Kim Piper Sandler.

我們的下一個問題來自——Do Kim Piper Sandler。

This is Skyler on for Do. For the partnership with MAI, do you have an update on how the soft launch is going for the DNA synthesis platform? And how near term is the plan to commercialize that in 2023? And can you comment on any expectations you have for that?

這是 Skyler 的任務。對於與 MAI 的合作，您是否有關於 DNA 合成平台軟啟動的最新信息？計劃在 2023 年將其商業化的時間有多短？你能評論一下你對此有什麼期望嗎？

So really, we look at the MAI partnership as a validation of the TDT enzyme and the technical capability of that enzyme. As Kevin said in his comments, a lot of it is around the ability to then tweak that to be part of the RNA platform. We think that MAI are making really great technical strides in terms of producing longer oligos. But we're waiting to see just like you are in terms of do they get commercial traction when they launch. So really, we're not planning on much right now. Kevin?

因此，實際上，我們將 MAI 合作夥伴關係視為對 TDT 酶和該酶技術能力的驗證。正如凱文在他的評論中所說，很多都是圍繞著將其調整為 RNA 平台一部分的能力。我們認為 MAI 在生產更長的寡核苷酸方面取得了巨大的技術進步。但我們正等著看，就像你一樣，他們在推出時是否會獲得商業吸引力。所以真的，我們現在沒有太多計劃。凱文？

No. We're being cautiously optimistic as associated with commercial uptake. We would like to see a little bit more in terms of their front-end pacing and their pull-through downstream. Again, we think they've achieved a really nice technical set of success here. So, we're waiting and seeing as you are.

不。我們對商業採用持謹慎樂觀態度。我們希望在他們的前端節奏和下游的拉動方面看到更多。同樣，我們認為他們在這裡取得了非常好的技術成功。所以，我們和你一樣在觀望。

Our next question coming from the line of Matt Hewitt with Craig-Hallum.

我們的下一個問題來自 Matt Hewitt 與 Craig-Hallum 的對話。

Maybe first, some clarification on the [Post-Covid] contribution. So, if I heard you correctly, there's still likely $12.5 million this year, next year, put it in Q4 if we're going to include it. I appreciate all of that. Will it still be -- will you still be recording that as revenues in the fourth quarter if and when it hits?

也許首先，對 [Post-Covid] 的貢獻進行一些澄清。所以，如果我沒聽錯的話，如果我們要將它包括在內，今年、明年仍然可能有 1250 萬美元放在第四季度。我很感激這一切。它仍然會——如果它來襲，你還會在第四季度將其記錄為收入嗎？

Yes, we would record that as revenue, but it would be noncash revenue.

是的，我們會將其記錄為收入，但它是非現金收入。

Okay. Got it. And then backing that off, so your guidance doesn't include it. If you look at the core product revenues in fiscal '22 compared to your guidance, it does appear as though your revenues are going to decline a little bit. Maybe a little bit of color on what's happening with the rest of the portfolio there.

好的。知道了。然後取消它，因此您的指導不包括它。如果您將 22 財年的核心產品收入與您的指導進行比較，您的收入似乎確實會有所下降。也許對那裡的其他投資組合發生的事情有一點顏色。

So, the low end of our revenue range of $63 million is flat to what we achieved in 2022, excluding tax loaded. I think what we've discussed that this is sort of a refocus year. We've talked about the variability in pharma manufacturing, how that ebbs and flows year-to-year, and we are expecting growth in Life Sciences to make up for that. That's how we came toward $63 million to $68 million range. So definitely a year where we are focusing for growth for life sciences that will set us up down the road.

因此，我們 6300 萬美元收入範圍的低端與我們在 2022 年取得的收入持平，不包括稅負。我認為我們所討論的是今年是重新聚焦的一年。我們已經討論了製藥製造業的可變性，以及它是如何逐年起伏的，我們預計生命科學領域的增長將彌補這一點。這就是我們如何達到 6300 萬至 6800 萬美元的範圍。因此，絕對是我們專注於生命科學增長的一年，這將使我們走上正軌。

Got it. And then maybe I think you've got 2 different groups that you're working with on commercial agreements at the moment. How should we be thinking about the structure of those contracts? Is it going to be simply hit your product sales line? Are these potential milestone royalty opportunities? Just trying to think about how they could end up impacting the financials.

知道了。然後，也許我認為您目前有兩個不同的小組正在就商業協議進行合作。我們應該如何考慮這些合同的結構？是否會簡單地打擊您的產品銷售線？這些是潛在的里程碑特許權使用費機會嗎？只是想想想他們最終會如何影響財務狀況。

So, with regards to the 2 different product lines, my assumption is you're talking about pharma manufacturing versus life sciences to clarify -- in that context,

因此，關於 2 條不同的產品線，我的假設是您在談論製藥製造與生命科學，以澄清——在這種情況下，

Yes, okay. Good, go ahead. No, I just said correct. I mean how are they going -- are those deals going to be structured where you'd be recognizing enzyme sales product sales? Or how will those 2 agreements be structured? Or what are your hopes there?

是的，好的。很好，繼續。不，我只是說對了。我的意思是他們進展如何 - 這些交易是否會在您認可酶銷售產品銷售的情況下進行結構化？或者這兩項協議將如何構建？或者你在那裡有什麼希望？

Yes. I mean I think it goes back to some of Stephen's comments earlier with regards to farm manufacturing and some of the challenges there in terms of selling enzyme supply and the lumpiness associated with that. When you're an intermediary associated with the biocatalysis process, we're definitely adding value there, but it's a little bit harder to negotiate downstream royalties, particularly with some of these larger pharmaceutical manufacturers. When you move over to life sciences where we can provide a really complex and differentiated enzyme, which really enhances the workflow, that hence, gets back to the larger range of revenue you can see from this type of opportunity because some of that is straight up product sales, but some of that also could be licensing fees as well as milestones and downstream royalties. And that's how we're looking at structuring those contracts going forward.

是的。我的意思是，我認為這可以追溯到斯蒂芬早些時候關於農場製造的一些評論，以及銷售酶供應和與之相關的塊狀物方面的一些挑戰。當您是與生物催化過程相關的中間人時，我們肯定會在那裡增加價值，但談判下游特許權使用費有點困難，尤其是與一些較大的製藥製造商。當你轉向生命科學時，我們可以提供一種真正複雜和差異化的酶，這真正增強了工作流程，因此，你可以從這種類型的機會中看到更大範圍的收入，因為其中一些是直截了當的產品銷售，但其中一些也可能是許可費以及里程碑和下游特許權使用費。這就是我們正在考慮構建這些合同的方式。

That's really helpful...

這真的很有幫助...

Thank you. The next question is from the line of Jacob Johnsons with Stevens.

謝謝。下一個問題來自 Jacob Johnsons 和 Stevens 的對話。

This is Mac on for Jacob. Just a couple of quick ones. Maybe for Sri. Can you talk about your priorities as it relates to balancing investment and managing cash burn? And how should we think about the outlook for R&D investments into this year?

這是 Jacob 的 Mac。只是幾個快速的。也許是為了斯里。你能談談你在平衡投資和管理現金消耗方面的優先事項嗎？我們應該如何看待今年的研發投資前景？

Sure, in terms of the loss, I think in the fourth quarter when we announced the restructuring plan, what we initiated was a more disciplined approach to the portfolio broadly where we were focused on high-potential development programs that had high-value commercial opportunities, and that's very much in line with how we've approached thinking about our 2023 and beyond investments. Cash burn is important to us. Certainly, we're starting the year in a strong cash position with $114 million that provides those 2 years of runway and funds the programs that we talked about on the call today, including moving 7108 forward gene therapy programs as well as RNA and DNA synthesis.

當然，就虧損而言，我認為在第四季度我們宣布重組計劃時，我們開始對投資組合採取更嚴格的方法，我們將重點放在具有高價值商業機會的高潛力發展項目上，這非常符合我們對 2023 年及以後投資的思考方式。燒錢對我們很重要。當然，我們以 1.14 億美元的現金頭寸開始了這一年，這些資金提供了這兩年的跑道，並為我們今天在電話會議上談到的項目提供資金，包括推進 7108 基因治療項目以及 RNA 和 DNA 合成.

So, my approach will be very much in line with that and ensuring that we are looking at the overall value that the programs are contributing to the company as opposed to just any one line item on the P&L. And then in terms of your question specifically on R&D expenses, we haven't provided expense level guidance. We provided the cash burn guidance. But what I will say, again, going back to the previous direction on refocusing the portfolio. We expect that the savings generated as a result of that effort will be redeployed to these new investments in high potential development programs. So hopefully, that helps a little bit.

因此，我的方法將非常符合這一點，並確保我們關注的是這些項目為公司貢獻的整體價值，而不是僅僅關注損益表中的任何一個項目。然後就您具體關於研發費用的問題而言，我們沒有提供費用水平指導。我們提供了現金消耗指南。但我要說的是，再次回到之前重新調整投資組合的方向。我們預計，通過這項努力產生的節餘將被重新部署到這些高潛力發展項目的新投資中。所以希望這能有所幫助。

Thank you for the color.

謝謝你的顏色。

Thank you. At this time, we've reached the end of our question-and-answer session. Now I'll turn the floor back to Stephen Dilly, Chief Executive Officer for closing remarks.

謝謝。至此，我們的問答環節已經結束。現在，我將把發言權轉回首席執行官斯蒂芬·迪利 (Stephen Dilly) 的閉幕詞。

Well, thanks, everyone, for tuning in today. As you can tell, we're very pleased with the results that we delivered in '22 and super excited for 2023 and continuing to make progress on these focus areas. So, thanks again, and have a great afternoon.

好吧，謝謝大家今天收看。如您所知，我們對我們在 22 年取得的成果感到非常滿意，並對 2023 年感到非常興奮，並繼續在這些重點領域取得進展。所以，再次感謝，祝你下午愉快。

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

今天的會議到此結束。此時您可以斷開線路。感謝您的參與。