Karyopharm Therapeutics Inc.

Good morning. My name is Jason, and I will be your conference operator today. At this time, I'd like to welcome everyone to the CarioFarm Therapeutics First Quarter 2021 Financial Results Conference Call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Ian Karp, CarioFarm's Senior Vice President, Investor and Public Relations.

Great. Thank you. And thank you all for joining us on today's conference call to discuss carrier farms, first quarter financial results and business update. And let me be the first one to officially welcome our new president and chief executive officer, Mr. Richard Paulson to our quarterly earnings call. This is Ian Karp. And today, in addition to both Michael Kaufman and Richard Paulson, I'm also joined by Mr. Mike Mason, our chief financial officer, Mr. John Demery, chief commercial officer, and Mr. Steven Michener, chief business officer. On the call today, Michael will provide an overview of key recent corporate developments and an update on our commercial progress, followed by an update on one of our key pipeline opportunities in endometrial cancer. Mike Mason will then provide an overview of the first quarter financial results. We will conclude with some thoughts from Richard on KaryoFarm's future, and then we will move to the Q&A portion of the call. Earlier this morning, we issued a press release detailing KaryoFarm's results for the first quarter of 2021 and the appointment of Richard Paulson as our next president and CEO. These releases, along with a slide presentation that we plan to reference on today's call, are available on our website at cariofarm.com. Before we begin our formal statements, I'll remind you that various remarks we make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and as outlined on slide number three. These include statements about our future expectations, clinical development and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations related to the commercialization of Expovio and Nexpovio, financial projections, and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factor section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. And when we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Michael Kaufman, co-founder of CarioPharm and our first CEO. And now please turn to slide number four.

Thank you, Ian, and good morning, everyone. Let me begin first by saying how thrilled I am to also be joined here today with Richard Paulson, our company's new CEO, and we'll begin on slide four. When Dr. Sharon Shackham and I started CarioPharm over 12 years ago, our mission was really quite simple. We wanted to do everything we possibly could to make a difference in the lives of patients battling cancer. More specifically, we sought to develop novel drugs that exploited a fundamental pillar of oncogenesis. namely the reactivation of tumor suppressor proteins by inhibiting their export out of the cell nucleus, which, as you may know, is actually where the name CarioPharm comes from. Now with our lead medicine, Expovio, having received three separate FDA approvals and one marketing authorization in Europe, over 450 employees and a robust pipeline of programs across both hematologic and solid tumor indications, I could not be more proud of the work we've accomplished on behalf of patients, their families, and healthcare providers. But as our company is increasingly focused on commercial execution and competing in the global cancer marketplace, the time is right for a new leader, particularly one with a strong track record for building successful oncology commercial brands. Richard, of course, is no stranger to Kariopharm, having served on our board of directors since February 2020. And prior to his new role here, Richard served as Chief Executive Officer of Ipsen North America and is the former Vice President and General Manager of Oncology at Amgen. Richard will provide some of his thoughts regarding Kario Farms' future at the end of today's review of our Q1 2021 earnings and business update. Please now turn to slide five. Total revenues were $23.3 million, with Expovio net product sales of $21.7 million in the quarter. Importantly, Expovio prescription demand increased 17% in Q1 2021, as compared to Q4 2020 following the expanded FDA indication granted in December of 2020. We also saw more than 160 new physicians or accounts prescribing Expovio for the first time in the quarter. This quarterly growth occurred when many myeloma brands were flat or declining. Moving to our pipeline progress, we recently announced that in March of 2021, the European Commission granted conditional marketing authorization for Nexpovio in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. Additionally, we also announced that we have now submitted the clinical data from our Phase 3 Boston study as part of a Type 2 variation marketing authorization application, formally requesting an expansion of our indicated label in Europe. This submission has now been validated, and we expect to have a decision on this application from the European Commission in the fourth quarter of 2021. Turning now to some other program updates from our ongoing hematological and solid tumor clinical studies, We are pleased to see the first set of data from our Phase III SEAL study evaluating Expobio in patients with de-differentiated liposarcoma were recently published, and the first patients have now been dosed in a Phase III study in diffuse large B cell lymphoma. Finally, on the financial front, we ended the quarter with a strong cash position of approximately $233.6 million that, along with expected future revenues, we anticipate will be sufficient to fund our planned operations into late 2022. Let's now turn to slide six, where I'll provide additional details on Expovio's recent sales performance. First quarter net Expovio sales increased by 7% as compared to the fourth quarter of 2020, while prescriptions increased by approximately 17%. This increase was primarily driven by multiple myeloma new patient starts. Additionally, we've seen strong payer coverage since the expanded approval we received from the FDA in December. I will note that much of the difference between the sales growth and prescription growth was driven by higher gross-to-net discounts, which are fairly typical in the first quarter of the year, as commercial and Medicare patients' out-of-pocket payment requirements reset for the new year. There were also some additional stocking within our distributor network at the end of 2020 in preparation for the launch of Expovio's expanded indication. While we expected higher demand growth, we are encouraged that sales and prescription demand returned to growth in the first quarter and we remain confident in Expovio's long-term commercial potential and our ability to further increase utilization. Richard's top priority in the coming weeks and months ahead of us will be to help our organization further accelerate the growth trajectory for Expovio in the U.S. market. We believe some of this will occur naturally, as we expect to see the benefit of longer duration of Expovio treatment in the second half of 2021, and we also believe our teams will have better access to customers in the second half of the year, which will increase promotional impact. Please now turn to slide seven. Here you can see a chart of monthly Expovio prescriptions for the first three months of 2021. Importantly, we saw a significant increase in March and we'll be working hard to further expand utilization and penetration into the earlier line treatment setting in the near future. Moving now to slide eight, the graph here shows the prescription refill rate for Expovio for both the first and second refills for those patients eligible for these refills. These numbers have remained encouraging throughout 2020 and into 2021 and are significantly higher as compared to our initial launch period in 2019. These refill rates, coupled with an average of nearly three treatment cycles per patient, further reinforce the positive feedback we've received from patients and physicians regarding their experience and uses of Expobio. Importantly, we do expect the average duration of treatment to increase throughout 2021 as more and more patients are being treated with a once-weekly Expovio dose and as part of a combination triplet regimen. Additionally, patient discontinuation rates due to side effects remains relatively low at 12%, which we believe is a testament to more and more physicians gaining comfort in helping their patients prevent and manage side effects from Expovio with proper prophylactic therapies and dose modifications. On slides 9 and 10, you can see our most current robust clinical development plan for Expobio in both hematological malignancies and solid tumors. This includes our phase 3 C endo study in patients with endometrial cancer, where we expect to have top-line data before the end of this year, and which I'll highlight in more detail in a few moments. I will note that there are two important clinical trials we expect to initiate in 2021, which we believe will help further define the broad clinical utility of Expovio as a potential partner of choice with other active anti-cancer agents. First, we expect to start a new randomized phase three study evaluating expofio in combination with pomalyst and dexamethasone in patients with previously treated myeloma that will begin in 2021. If the results of this trial are positive, this regimen could represent a potent all-oral drug option to patients with refractory myeloma. Next, we plan to initiate a new phase two study evaluating expofio in combination with ketrudib in patients with newly diagnosed or recurrent metastatic melanoma. We're particularly excited about this study based on some encouraging data from an investigator-sponsored trial from MD Anderson evaluating this combination regimen, which was presented at the annual ESMO conference in 2020. Moving to slide 11, I'll highlight the potential opportunity of expovia on patients with endometrial cancer, where we're currently conducting our phase 3 SIANDO study. Endometrial cancer is the most common gynecologic cancer in the U.S., with over 65,000 new cases and, unfortunately, over 12,000 new deaths in 2020. While most women are diagnosed with early stage disease and have a good prognosis after surgery alone, approximately 14,000 patients each year in the United States have advanced or metastatic disease and are treated with combination chemotherapy in the frontline setting. When their disease progresses, these patients are typically treated with additional chemotherapy, immunotherapy, and or targeted agents. However, currently, there are no approved drugs in the maintenance setting for patients who've had a response to their frontline chemotherapy. This is the setting in which we're currently studying Expobio in the Siendo study. A similar approach was taken with PARP inhibitors for patients with ovarian cancers, and their use in this maintenance setting in that disease has been quite dramatic. To put our potential opportunity in endometrial cancer in perspective, assuming about two-thirds of frontline patients respond to chemotherapy, there could be 3,000 or so patients treated each year in the maintenance setting by capturing approximately 30% of this market. Now, as we move to slide 12, you will see highlights from a previous phase 2 study published in 2019, which evaluated Selenexer in 114 patients with heavily pretreated and actively progressing gynecologic cancers. including 23 patients with heavily pretreated endometrial cancer who previously received a median of two and up to five fire lines of therapy. In this population with growing cancer, patients treated with single-agent selenexer demonstrated a disease control rate of 35% and a confirmed partial response rate of 9%. The most common side effects were similar to other cell and extra studies and included nausea, fatigue, decreased appetite, vomiting, weight loss, anemia, thrombocytopenia, dysgousia, and blurred vision, and were primarily grades one and two and reversible. On the right-hand side of the slide, you can see a waterfall plot of the best percent change in the sum of all the target lesions from screening for 19 evaluable patients with endometrial cancer. This encouraging clinical data in a population with highly refracted progressive endometrial cancer gave us the confidence to conduct the Ciendo study in the frontline maintenance setting, which is summarized on slide 13. Ciendo's enrolled in approximately 248 patients, randomized two to one, to receive either 80 milligram Selenex or once weekly or matching placebo. Eligible patients included those who have completed a single line of at least 12 weeks of Taxane-Platinum combination chemotherapy and achieved either a partial or complete response. The primary endpoint of the trial is improvement in progression-free survival from the time of randomization until death or disease progression. In November of 2020, we announced the trial had passed its planned interim futility analysis, and so the study continues as planned with no modifications, and we expect the top-line data by the end of this year. We remain highly encouraged by this study and the opportunity for patients should the trial meet its primary endpoint, and we look forward to providing additional updates in the future. With that, I'll now turn the call over to Mike Mason to review the quarterly financials. Mike? Thank you, Michael.