Hello, and welcome to Regeneron Pharmaceuticals' Third Quarter 2022 Earnings Conference Call. My name is Tawanda, and I will be your operator for today's call. [Operator Instructions] Please note that this conference is being recorded.

I would now like to turn the call over to Ryan Crowe, Vice President, Investor Relations. You may begin.

Ryan Crowe - Vice President, Investor Relations

Thank you, Tawanda. Good morning, good afternoon and good evening to everyone listening around the globe. Thank you for your interest in Regeneron and welcome to our third quarter 2022 earnings conference call. An archive of this webcast will be available on our Investor Relations website shortly after the call ends. Joining me today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Executive Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include, but are not limited to those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition. These forward-looking statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statements. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended September 30, 2022, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise.

In addition please note that GAAP and non-GAAP measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release, which can be accessed on our website. Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

With that, let me turn the call over to, our President and Chief Executive Officer, Dr. Len Schleifer. Len?

Leonard Schleifer - President and Chief Executive Officer

Thank you, Ryan, and thank you to everyone joining today's call. Regeneron's strong operational momentum continued in the third-quarter highlighted by important developments across our pipeline and outstanding commercial execution. Total revenues for the quarter increased by 11% compared to last year when excluding contributions from our COVID antibody cocktail, with global net sales of Dupixent and Libtayo, as well as U.S. net sales of EYLEA once again reaching new all-time quarterly highs and growing by double-digits.

Before diving deeper into our commercial results, I'd like to review some of the recent progress we have made across our pipeline, starting with the striking pivotal data that we reported in September for our investigational aflibercept 8 mg, which we believe could ultimately transform the treatment landscape for patients. With nearly 90% of DME patients and 80% of wet-AMD patients able to sustain 16 weeks maintenance dosing through 48 weeks of treatment, we believe aflibercept 8-milligram may shift the current treatment paradigm with more patients receiving less-frequent injections, while achieving visual acuity gains, anatomical improvements and a safety profile comparable to EYLEA.

It has proven to be very difficult to decrease the treatment burden beyond what we were able to achieve with EYLEA over a decade ago with many potential treatments failing either due to sub-optimal visual outcomes or safety issues. A recently approved anti-VEGF agent did not demonstrate in pivotal studies that the majority of patients in either disease were able to sustain 16-week maintenance dosing throughout the first year of treatment. Supporting our view that aflibercept 8-milligram has the potential to become the next-generation standard-of-care, anti-VEGF treatment assuming regulatory approval.

We plan to submit the aflibercept 8-milligram pivotal data to the FDA under a single BLA at the end of this year and have decided to use a previously granted priority review voucher to expedite the FDA review process. Pre-launch planning is already underway with the potential FDA approval by late August 2023. In addition to the pivotal aflibercept 8-milligram data, Regeneron continue to make notable progress in our immunology and oncology pipelines. Starting with immunology, in September we received FDA approval for Dupixent in prurigo nodularis, the first systemic therapy for this indication and the fifth disease for which Dupixent is now approved. So far this year, Dupixent has received four U.S. or EU regulatory approvals, expanding the treatment-eligible population by approximately 225,000 patients, including in two diseases that previously had no FDA-approved systemic therapies.

In the first half of next year, we are looking forward to EU regulatory decisions for eosinophilic esophagitis, prurigo nodularis and atopic dermatitis in patients as young as six months. With these potential additional indications, approximately 200,000 more patients with these type two inflammatory diseases could benefit from Dupixent's unmatched clinical profile. Additionally, we expect pivotal data readouts for Dupixent in chronic inducible cold urticaria and chronic obstructive pulmonary disease in the first half of next year.

Moving to oncology with the depth and breadth of our pipeline has positioned Regeneron to ultimately become a global leader. We presented several datasets at this year's European Society for Medical Oncology Annual Meeting, further underscoring the importance of Libtayo as the foundation for our overall oncology strategy. George will review the data in more detail during his remarks, but we were particularly encouraged by the results for Libtayo monotherapy in neoadjuvant CSCC, as well as Libtayo in combination with fianlimab our LAG-3 antibody in first-line metastatic melanoma.

We also presented monotherapy data for our MUC16xCD3 bispecific in recurrent ovarian cancer, which has the potential to be combined with Libtayo, as well as data for our METxMET biparatopic bispecific antibody, in MET-altered non-small cell lung cancer. I'd also note the early, but very exciting results for our PSMAxCD28 costimulatory bispecific in combination with Libtayo, which show promising anti-tumor activity in patients with advanced metastatic castrate resistant prostate cancer. The patients enrolled in our study have a poor prognosis with an expected survival of one to two years depending upon their treatment history. Given prostate cancer has been largely unresponsive to PD1 inhibition and immunotherapy in general, there is a clear need for new treatments. In 2020 alone, there were over 375,000 deaths globally from prostate cancer and it was the second leading cause of cancer death in American men.

We continue to expand our costimulatory bispecific efforts in prostate cancer with an acceleration in enrollment in our first-in-human study since we reported our top-line results in August and we look forward to updating you on this program in the first half of next year.

Now, turning to our commercial performance. In the third-quarter EYLEA global net sales grew 8% at constant currency to $2.4 billion. In the U.S. EYLEA net sales were $1.63 billion, up 11% year-over-year and outperforming the anti-VEGF category growth of only 4%. Despite recent branded and biosimilar entrants, EYLEA is setting new all-time high for anti-VEGF category share in the United States. Dupixent continued to grow at a remarkable pace posted by approvals in new diseases and younger patient populations in previously approved indications. In the third-quarter global net product sales were $2.3 billion, up 45% at constant currency compared to last year, reflecting growth across all indications and all geographies.

Dupixent's differentiated clinical profile and ability to effectively treat more-and-more patients in both currently approved indications and potentially for additional type two inflammatory diseases is expected to drive strong growth in the future. Libtayo total net sales grew 25% globally at constant currency $243 million in the third-quarter, including 21% growth in the United States, driven by non-melanoma skin cancer indications and monotherapy non-small cell lung cancer. At the start of the third-quarter, we acquired global rights to Libtayo from Sanofi. With potential future combinations including with chemotherapy in non-small cell lung cancer as well as other pipeline agent in development. We believe Libtayo is poised to become a more meaningful revenue contributor over time.

We are excited about the strong commercial performance for our core products, the compelling efficacy, safety and durability data that we reported for aflibercept 8 milligrams as well as the notable progress we have made advancing our pipeline, particularly in oncology. Our pipeline now includes approximately 35 product candidates in clinical development, including a number of marketed products that we're investigating for additional indications, some of which George will discuss in a moment.

In closing, our strategy continues to focus on investing in our internal R&D capabilities, while exploring potential collaborations that will enable us to fully realize the power of our science. We remain confident in this strategy and in our growth prospects, as well as in our ability to deliver breakthroughs to patients and value to shareholders.

Now, I'll turn the call over to George.

George Yancopoulos - President and Chief Scientific Officer

Thank you, Lynn. I'll start with ophthalmology. Positive pivotal results for aflibercept 8 milligrams in the PULSAR and PULSAR studies we recently presented at the American Academy of Ophthalmology Annual Meeting. The results of these trials in wet AMD and DME, respectively, demonstrated that a remarkably high percentage of patients were able to be rapidly initiated into and then successfully maintained through week 48 on 12- and 16-week dosing intervals. While achieving vision gains that were not inferior to the current standard of care, EYLEA 2-milligram dose every 8 weeks. These results suggest that aflibercep 8 milligrams has the potential to become the new standard of care in these retinal diseases.

I think it would be helpful if we step back for a minute and try to put these results in context. While what our trials did was push the limits far beyond what has been accomplished with any currently available anti-VEGF therapies. Rather than using response criteria to try to identify or slowly extend patients to longer dosing intervals, our trials tested whether all patients could be randomly assigned and rapidly initiated on extended dosing intervals of aflibercep 8-milligram without compromising visual improvement or safety. These aflibercep 8-milligram trials accomplished just that for the vast majority, while delivering a safety profile consistent with that of EYLEA. 89% of DME patients and 77% of WED AMD patients were able to be rapidly initiated and maintained on a 16-week of aflibercep 8-milligram dosing regimen, while 93% of DME and 83% of wet AMD patients we're able to be rapidly initiating maintained on at least a 12-week dosing interval, all while delivering efficacy similar to that of EYLEA administered every 8 weeks.

We believe these are truly unprecedented and potentially game-changing results, which have not been achieved using any other anti-VEGF agent. Now this has speculated that our PULSAR and PHOTON results were due to our dose modification criteria and even try to theoretically extrapolate that their agent could have somehow approached these results using our criteria. We put these speculative extrapolations into the category of wishful thinking. And based on our expert analysis of the data, we conclude it is all about the drug and not the trial design.

Briefly moving on to Dupixent. Building on our recent approval in eosinophilic esophagitis in adults and adolescents, we are planning on submitting a supplementary BLA for eosinophilic esophagitis in 1 to 11-year-old children in mid-2023. Dupixent ability to treat eosinophilic esophagitis highlights how important it is that our IL-4 and IL-13 blocker more completely targets the entire type two inflammatory cascade and not only eosinophils.

As you heard Len mentioned, the FDA label was expanded yet again in the third quarter as Dupixent became the first and only treatment indicated for prurigo nodularis, a debilitating chronic skin disease. This marks the fifth disease for which Dupixent is now approved. Our collective clinical data with Dupixent support a unifying molecular mechanism underlying these related diseases from asthma to atopic dermatitis to nasal polyps to prurigo nodularis to eosinophilic esophagitis. In this unifying hypothesis, IL-4 and IL-13 induced inflammation is driving all of these related diseases in different tissue compartments.

Moving to Libtayo in oncology. In the third quarter, our robust oncology pipeline has started to deliver data readouts from our latest and most innovative programs and we are expecting these readouts to accelerate in the remainder of 2022 and continuing to 2023. The European Society of Medical Oncology, or ESMO Annual Meeting in September, was truly a banner event for Regeneron with several notable oral presentations for assets in our oncology pipeline, which I'd like to briefly summarize.

Starting with fianlimab, our LAG-3 antibody in combination with Libtayo. At ESMO, we shared data from two independent advanced melanoma expansion cohorts from our first-in-human study, which importantly showed consistent efficacy and safety between the two replicate cohorts. Fianlimab, in combination with Libtayo demonstrated greater than 60% response rates in each cohort, a median PFS estimated to be 24 months across both cohorts and a median duration of response that had not yet been reached. The preliminary safety profile of the combination appears to be in line with anti-PD-1 monotherapy and potentially with less toxicity compared to anti-CTLA-4 combinations.

While dual LAG-3 and PD-1 inhibition has previously shown promise in advanced melanoma, response rates greater than 45% with median PFS of more than a year had not been previously reported. These initial results in melanoma suggest that fianlimab-Libtayo combination has a potentially best-in-class profile in this setting. We are enrolling our Phase 3 metastatic melanoma study - we intend to initiate a Phase 3 adjuvant melanoma study later this year and have additional plans in other solid tumors where fianlimab has the potential to be first-in-class.

In neoadjuvant cutaneous squamous cell carcinoma, or CSCC, a Phase 2 study of Libtayo monotherapy has shown promising results. Given prior to potentially curative surgery in patients with large tumors, Libtayo was able to deliver major pathological responses to 63% of patients prior to surgery. This raises the possibility that Libtayo could decrease the burden of these major and potentially disfiguring surgeries for the many patients who require them each year. We are pleased that concurrent with the ESMO presentation, these data were published in the New England Journal of Medicine.

Regarding next steps, we are talking to regulators about possible pathways for labeling and potential inclusion in the NCCN guidelines. Also at ESMO, we presented initial clinical data for ubamatamab, our MUC16xCD3 bispecific developed for advanced ovarian cancer. Our first clinical data for a CD3 bispecific in a solid tumor. In a heavily pretreated ovarian cancer population, we observed durable responses to this MUC16xCD3 monotherapy in a patient subset whose tumors overexpressed MUC16, response rates were as high as 31%. Most of the treatment of Vergent [Phonetic] adverse events occurred with the initial step-up dosing. Ubamatamab is being developed as a monotherapy as well as in combination with Libtayo as well as in combination with our MUC16 costim bispecific. We are looking forward to more data across these programs in 2023.

In our ESMO investor presentation, we shared more detailed data for PSMAxCD28 costim bispecific in combination with Libtayo representing the first efficacy and safety data for this new class of bispecifics, which we had initially top-lined and discussed at our second quarter earnings. We have since continued to enroll patients in this study, and we are planning to present updated data at a medical meeting in the first half of 2023.

Regarding our hem/onc pipeline, we are looking forward to data from odronextamab, our CD20xCD3 bispecific as well as limboseltamab, our BCMAxCD3 bispecific at the American Society of Hematology or ASH Annual Meeting in December. For otrenixtimab, we will present pivotal Phase 2 data for both follicular lymphoma and diffuse large B-cell lymphoma in two separate oral presentations. Upon discussions with the FDA, we are now targeting a second half 2020 regulatory filing for this program. We hope to initiate combination studies with an appropriate CD20 costim bispecific in the near future.

For limbaceltumab, our BCMAxCD3 bispecific antibody remained on track with development and are planning to file pending discussions with the FDA in 2023. We have now completed enrollment in our potentially pivotal Phase 2 study. As I mentioned earlier, data from this study will be updated at ASH.

As with otrenixtimab, we are planning on initiating combination studies for limboseltumab with costimulatory bispecifics in the near future. We believe existing standard-of-care therapies leave significant room for improvement in these difficult-to-treat settings, and we have been encouraged by the interim efficacy and safety data we have generated to date for both odronextamab and limboceltimab.

Finally, at ESMA, we also shared initial data for our METxMET bispecific antibody in MET-altered non-small cell lung cancer. Responses were enriched in patients with higher levels of met expression. No dose-limiting toxicities were observed. Even the modest overexpression of MET may render lung cancer susceptible to this mechanism of action and we're looking forward to the METxMET antibody drug conjugate data next year.

In summary for oncology, a rich commentatorial pipeline is delivering competitive data. And with our full ownership of Libtayo, we're excited about the potential to advance standard of care in oncology with our portfolio approach.

Concluding with the Regeneron Genetic Medicines efforts, where we continue to progress our pipeline and discovery engine. In September, we and Alnylam reported promising data from our ongoing Phase 1 study of Alnylam HSD in nonalcoholic steatohepatitis or NASH. We are planning on initiating a Phase 2 study shortly, which is just one part of our multipronged approach, exploring multiple genetically validated targets for NASH.

Also in September, we and Intellia announced initial data from the cardiomyopathy arm of our ongoing Phase 1 study of NTLA-2001, an investigational CRISPR-based therapy for the treatment of transthyretin amyloidosis, which show deep and sustained mean serum TTR reductions of over 90% and was generally well tolerated. Finally, in October, our collaborators a Decibel Therapeutics announced FDA clearance for an NDA application for DB-OTO, our first virally delivered gene therapy product candidate designed to provide hearing to individuals with autoferalin-related hearing loss. This IND provides clearance to initiate a pediatric Phase 1/2 clinical trial in the United States.

With that, I will turn it over to Marion.

Marion McCourt - Executive Vice President, Head of Commercial

Thank you, George. Our third quarter performance reflects strength in growth across our commercial portfolio. We continue to extend our leadership position in additional therapeutic categories as part of our commitment to deliver life-changing medicines to patients in need. With Dupixent's approval in prurigo nodularis, Libtayo's anticipated approval in combination with chemotherapy in first line advanced non-small cell lung cancer and recent data demonstrating the compelling profile of aflibercep 8-milligram Regeneron's commercial business is poised to deliver long-term growth.

Starting with EYLEA, which reached $2.4 billion in global net sales for the third quarter. This represents an 8% increase on a constant currency basis, a remarkable achievement for a brand that launched 11 years ago. In the U.S., EYLEA net sales grew 11% year-over-year to $1.63 billion to again achieve over 1 million injections in the quarter. Despite the overall 2% sequential category decline in volume from the second to third quarter of 2022, EYLEA continued to grow across all indications, gaining share from both branded and unbranded agents. In fact, EYLEA reached all-time highs in category share of approximately 50%, with a commanding 75% share in the branded category. We continue to strengthen and extend EYLEA's leadership position in the anti-VEGF category.

As we recently announced, the FDA has granted pediatric exclusivity for EYLEA, thereby extending the period of EYLEA U.S. market exclusivity by an additional six months through May 17, 2024. Since announcing positive Phase 3 results earlier this year, there's been widespread excitement in the retina community about the aflibercep 8-milligram data set and aflibercep 8 milligrams potential to become the future standard of care if approved.

Next to Libtayo. Total global product sales were $143 million, growing 25% on a constant currency basis. In the U.S., net sales grew 21% to $95 million based on growth in our lung and non-melanoma skin indications. We see particular opportunity for growth in lung cancer over time. In monotherapy, there are already steady increases in prescribers and total utilization. We are launch-ready for the potential chemotherapy combination approval, which significantly expands the patient opportunity.

And finally, to Dupixent, third quarter global net sales were $2.3 billion, up 45% on a constant currency basis. In the U.S., net sales grew 45% to $1.82 billion, driven by robust demand across atopic dermatitis, asthma and nasal polyps. Growth was also driven by a rapid launch trajectory across recent indications, including eosinophilic esophagitis and pediatric atopic dermatitis where Dupixent is the only biologic to be approved from infancy through adulthood. Starting with dermatology and atopic dermatitis, Dupixent is the leading first-line systemic therapy with strong uptake across the spectrum of moderate to severe disease and across age groups. The ongoing launch in children as young as six months is progressing very well, providing relief to children and their families as well as reinforcing the safety of Dupixent for all age groups.

We have also expanded Dupixent's leadership in dermatology following its approval in prurigo nodularis. Dupixent is the only FDA-approved medicine for this chronic debilitating skin disease that affects approximately 75,000 adults in the U.S. Early launch indicators are positive with patients already being initiated on therapy.

Dupixent also continued to perform well in the highly competitive asthma market with steady growth in prescriptions and new patient starts as well as in nasal polyps. Early launch performance in the eosinophilikc esophagitis has been very strong, with broad adoption from both gastroenterologists and allergists. The medical community has embraced Dupixent as patients previously had very limited options Dupixent is the only medicine indicated to treat eosinophilic esophagitis and is the only treatment shown to address the underlying disease causes resulting in unprecedented symptom relief.

There are approximately 50,000 adults and adolescent patients in the U.S., and we continue to advance our clinical efforts in younger patients where substantial unmet need remains. Outside the U.S. Dupixent net sales were $506 million, growing 44% on a constant currency basis. There is rapid uptake across approved indications, and we continue to execute on recent launches and expand into new geographies. As part of this, Regeneron's increased presence in key international markets supports efforts to bring Dupixent to even more patients.

In conclusion, our third quarter performance demonstrates strength and growth across our commercial portfolio. We are successfully executing on initiatives to deliver life-changing medicines to patients and advancing strategies to maximize new and upcoming launches. Our commercial portfolio is positioned well to drive long-term and sustainable growth.

Now I'll turn the call to Bob.

Robert Landry - Executive Vice President and Chief Financial Officer

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron performed well in the third quarter, with growth from key brands and execution across the business, continuing to drive strong financial results on both the top and bottom line. Excluding global revenues related to the COVID-19 antibody cocktail, third quarter total revenues increased 11% year-over-year to $2.9 billion, demonstrating continued growth momentum from our core business and reflecting the favorable impact of the Libtayo transaction.

Third quarter total diluted net income per share was $11.14 on net income of $1.3 billion. Beginning with collaboration revenue and starting with Bayer. Third quarter 2022 ex.-U.S. EYLEA net product sales were $817 million, up 4% on a constant currency basis versus third quarter of 2021. Total Bayer collaboration revenue was $333 million, of which $315 million related to our share of EYLEA net profits outside the U.S. Total Sanofi collaboration revenue was $711 million in the third quarter of 2022 and grew 22% from the prior year, driven by Dupixent.

Recall that in connection with the Libtayo transaction, we increased the repayment of our antibody collaboration development balance from 10% to 20% of antibody collaboration profits. A portion of this step-up is recorded as a reduction to antibody collaboration revenues, while another portion is recorded as R&D expense. Given Regeneron is now recording its full 50% share of antibody collaboration R&D expense as incurred. Previously, Regeneron had only recognized a partial share of its antibody collaboration R&D expenses as incurred, with the remaining share of expenses added to the antibody development balance.

Also, as we highlighted last quarter and in accordance with the agreement, we recorded a onetime development balance repayment of $57 million as an incremental reduction to Sanofi collaboration revenue in the third quarter of 2022. We have posted to our website supporting materials to further explain the accounting associated with this and other elements of the Libtayo transaction.

Moving now to our operating expenses. R&D increased 38% year-over-year to $817 million, partially driven by the impact of the Libtayo transaction, which affects R&D in two ways. First, Regeneron now records all R&D expense for Libtayo, which was previously shared equally with Sanofi. Second, as I mentioned earlier, Regeneron now records our full 50% share of antibody collaboration spend for Dupixent and itepekimab.

SG&A expense increased 20% year-over-year to $467 million, primarily driven due to incremental costs related to assuming global rights to Libtayo. Cost of goods sold in the third quarter was $109 million, and product gross margin in the quarter increased to 94% as compared to 90.2% in the prior year. The more favorable gross margin was driven by the nonrecurrence of REGEN-COV sales in the current period and the removal of the payment to Sanofi for their share of U.S. Libtayo gross margin. Finally, the third quarter 2022 effective tax rate was 12.1% compared to 10.8% in the prior year.

Shifting now to cash flow and the balance sheet. Year-to-date in 2022, Regeneron has generated $2.9 billion in free cash flow and ended the third quarter of 2022 with cash and marketable securities less debt of approximately $10.3 billion. We remain focused on leveraging our strong financial position to deliver long-term value for shareholders. Over the first nine months of 2022, we have deployed in excess of $2.8 billion in capital. We have executed approximately $1.2 billion in business development initiatives, including the $900 million acquisition of Libtayo rights. Additionally, we have repurchased over $1.6 billion of our shares, including over $900 million in the third quarter alone. As of September 30th, we had approximately $1.2 billion remaining on our current share repurchase authorization, and we remain opportunistic buyers.

As we approach the end of the year, we've made some minor changes to our 2022 guidance ranges. A complete summary of our latest full year financial guidance is available in our press release issued earlier this morning. In addition to these changes, I would also like to provide some initial thoughts on our 2023 expense outlook. We continue to make investments to advance our pipeline and position the company for long-term growth. We expect R&D investment to grow in 2023 comparable to or slightly above the nine-month year-to-date growth rate reported earlier today. The incremental R&D investment in 2023 will be driven by advancing our immuno-oncology, hematology, immunology and genetics medicine pipeline as well as the continued expansion of our R&D organization.

In addition, 2023 will be the first full year reflecting the impact of the Libtayo transaction, where we record 100% of the global R&D spend for Libtayo and our full 50% share of the Sanofi antibody collaboration R&D spend as incurred. For SG&A in 2023, we currently project growth in the mid-teens versus 2022, given we'll be recording a full year of global Libtayo expenses, along with targeted investments in the build-out of our international infrastructure.

Finally, for other operating income and expense in the third quarter of 2022, we recognized the remaining $44 million of deferred income related to previously received upfront payments and development milestones for fasinumab as a result of the program's discontinuation. We do not currently expect any material other operating income or expense in the fourth quarter of 2022, in 2023 and beyond absent any new transactions.

In conclusion, Regeneron has performed exceptionally well in the first nine months of 2022, and our strong financial position enables continued investment to drive long-term growth.

With that, I will pass the call back to Ryan.

Ryan Crowe - Vice President, Investor Relations

Thank you, Bob. Towanda, this concludes our prepared remarks. We'd now like to open the call for Q&A with the number of callers in the queue, I'd like to ensure we are able to address as many questions as possible. As a result, we'll only be able to answer one question from each caller before moving to the next. Towanda, please open the call for Q&A.

Question & Answers

Operator

[Operator Instructions] Our first question comes from the line of Evan Seigerman with BMO. Your line is open.

Evan Seigerman - BMO Capital Markets - Analyst

Hi, guys. Thank you so much for taking my questions and congrats on the progress. So with nearly $13 billion on the balance sheet and minimal debt. Can you provide more color on your capital allocation priorities? Would you consider business development on a larger scale and are issuing a dividend?

Robert Landry - Executive Vice President and Chief Financial Officer

Evan, hi. Good morning, it's Bob. With regards to capital allocation, demonstrated today by our growth in R&D and the 2023 forward guidance, we are going to continue to invest, first and foremost, in the R&D pipeline that we have. We issued our 10-Q this morning, within the MD&A, you'll see a plethora of trials that are currently ongoing. And as George mentioned in his script, we're very bullish with regards to what is in the pipeline. Now again, with regards to business development, it's not an end or an or, right? As you saw and what we've done in the first nine months of 2022, where we do think there are opportunities and where we do think we can do collaborations where one plus one is 3, then we're absolutely going to take that opportunity. And I think Checkmate was a good example of that. And I would expect that you'd see more of that.

With regards to your question on dividends, it's never a never. Obviously, that tool is in our tool chest. If we do decide to play that card as of right now, we don't have dividends in the foreseeable future in our plan. We have been very opportunistic with regards to buybacks. Again, the MD&A issued earlier today. The 10-Q will show you what we've been buying back our shares. Again, we'll remain opportunistic buyers, and we do have a remaining $1.2 billion remaining under our current $3 billion authorization.

Ryan Crowe - Vice President, Investor Relations

Thanks, Bob. Towanda, please have the next question on, please.

Operator

Thank you please standby for our next question. Our next question comes from the line of Tyler Van Buren with Cowen. Your line is open.

Tyler Van Buren - Cowen and Company - Analyst

Hi, guys. Good morning. Congratulations on a great quarter. So I just pulled up the odronextamab and 5458 ASH abstracts. And It'd be great to get a brief preview from you guys and what you need - what you believe you ultimately need to show at the conference to be competitive relative to what others have shown.

Leonard Schleifer - President and Chief Executive Officer

I don't think we want to stoop ourselves given that the conference is coming up pretty soon, Tyler. But odronextamab has the potential of being a very important molecule. We recognize that there are some people ahead of us. And we recognize that some of the most recent timelines have pushed back a little bit based on recent regulatory feedback. The regulators have recently been focused on having Phase 3 trials substantially enrolled at the time of submission before they'll grant accelerated approval. But we are confident in the profile of odronextamab and as George says, there's also the future possibility of combinations with other things in our pipeline that could really even lead for us.

Ryan Crowe - Vice President, Investor Relations

Thanks, Len. Next question please, Tawanda.

Operator

Thank you. Please standby for our next question. Our next question comes from the line of Salveen Richard with Goldman Sachs. Your line is open.

Salveen Richter - Goldman Sachs - Analyst

Good morning. Thanks for taking my question. On EYLEA, what are you observing in the market between yourselves and Roche for the potential launch?

Marion McCourt - Executive Vice President, Head of Commercial

So happy to give more characterization. As I mentioned, we see EYLEA continuing to perform extremely well, reaching all times high, category share 50% and now as well growth in the overall branded market where we participate with other branded agents, including Roche. One thing I will mention, just to give a bit more insight is that EYLEA captured growth coming primarily from Lucentis and also from Avastin. And in fact, if you put the Roche portfolio together, the growth of EYLEA, obviously, was positive, while there was a decline in overall market share for the Roche products combined.

Ryan Crowe - Vice President, Investor Relations

Thank you, Marion. Next question Tawanda.

Operator

Thank you. Please standby for our next question. Our next question comes from the line of Matthew Harrison with Morgan Stanley. Your line is open.

Matthew Harrison - Morgan Stanley - Analyst

Great. Good morning. Thanks for taking the question. George, I was wondering if you could just comment on your outlook for the COPD study for Dupixent and how you think about that market opportunity. Thanks.

George Yancopoulos - President and Chief Scientific Officer

Obviously, COPD has been a very difficult disease for new therapies in biologics, in particular, we think that there's a category of patients with COPD who have or are marked by more what we call Th2 type inflammation. We think that, as I said in my remarks, that there's this unifying hypothesis that there are a lot of Th2 type of diseases that manifest in different ways. We believe that this subset of patients with COPD may, maybe or fit into that category and being able to benefit these patients in terms of either reducing their exacerbations and/or improving their lung function would really make a difference to these patients. And so we're anxiously awaiting the data, and we're hopeful that we will have another set of patients where we might be able to demonstrate that Dupixent could really make a difference.

Ryan Crowe - Vice President, Investor Relations

Thanks, George. Tawanda, next question.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Tim Anderson with Wolfe Research. Your line is open.

Tim Anderson - Wolfe Research - Analyst

Thank you so much. Lilly will be launching lebrikizumab in '23 in atopic derm and they have data that looks comparable to Dupixent, at least in this one indication, pretty much a direct competitor although not identical on mechanism. They know the derma space because of Taltz and the positioning is going to be that they can dose every month versus Dupixent, which is every two weeks. So I'm wondering if you have any strong views on that product, or if you think there's going to be a total non-starter, which is pretty much the consensus view? Thank you.

Leonard Schleifer - President and Chief Executive Officer

Maybe Mary can comment on it. But look, there's room for competitors in this market. we're really modestly penetrated in the opportunity. I don't think that the profile of what you say is actually going to be so far as we've seen it so far, they're all that similar, we have the earliest from infancy already to adult. That's a big deal, okay? In addition, the fact that many of these people have other comorbidities whether it be asthma or nasal polyps, for example, and they can get - if they do have comorbidities, a single drug can treat both is a very big differentiator.

So I think when you're the market leader, when you're so far ahead when you have really a differentiated profile, you have an advantage. Obviously, Lilly is a fine company. They know what they're doing. But as I said, there's room frequently when new good drugs come to market, there is a growth of the market. We're not going after a fixed number of patients. We're actually growing those patients. Marion, I don't know if you want to add anything.

Marion McCourt - Executive Vice President, Head of Commercial

I would just add that most of the key opinion leaders that we speak to recognize that the dual mechanism of action, the anti-IL-4 coupled with anti-IL-13 is very, very important. So certainly, efficacy shouldn't be assumed. There's also reinforcement of the incredible efficacy that's seen for patients with moderate through severe disease. And obviously, real-world experience is compelling. The administration with Dupixent is really quite straightforward. It's self-administration, and we actually see there the active patient or parent involvement has been very helpful in establishing Dupixent. But certainly, as Len mentioned, expanding the education in category to bring more atopic dermatitis patients into the treatment continuum is very positive for patients and certainly for Dupixent.

George Yancopoulos - President and Chief Scientific Officer

Not to pile on, but since - just to add on to what Len was saying. I mean, the fact that the IL-13 have failed in these other important Th2 inflammation-driven diseases like asthma and like COPD and others right now, really does suggest that they are not fully addressing the Th2 inflammation both in any one particular disease, but also, as Len said, so many of these individuals, if you just look at our label or any label that describes these diseases, they suffer from other allergic comorbidities.

And so, obviously, you can make such a difference for a patient where one drug can treat a systemic disease as opposed to treating the disease only in one of the many compartments where it manifests itself. I think this is the way I think medicine in the field should be moving. This is a systemic disease where Th2 inflammation is probably ramping in many compartments in the body you don't only want to treat it in one compartment, you want to treat the entire body. And that's what we've been showing systematically by going one disease after another with Dupixent. It works in every compartment and it broadly attacks the underlying inflammation that's related and causative in all of these diseases.

Ryan Crowe - Vice President, Investor Relations

Okay. Thank you for that response. Towanda, can we go to the next question?

Operator

Thank you. Please standby for our next question. Our next question comes from the line of Mohit Bansal with Wells Fargo. Your line is open.

Mohit Bansal - Wells Fargo - Analyst

Great. Thanks for taking my question and congrats on the progress. If I could probe a little bit further on the comments you made about the growth of anti-VEGF market, you said it's about 4% year-over-year, seems like a bit of a slowdown from what the high growth we have seen. Could you elaborate it further, do you see - just one quarter, do you see any underlying trend there? And is it because of the high growth we saw post-COVID, which is tapering down? If you could help us understand that. Thank you.

Marion McCourt - Executive Vice President, Head of Commercial

I think it's very difficult to extrapolate one quarter. Certainly, I did mention that there had been a sequential decline of about 2% going from the second quarter into the third quarter in the overall anti-VEGF category, but I think it's really difficult to extrapolate from that. The numbers you shared on overall year-over-year growth of category at about 4%, we recognize as well, I think we'll have to see as a bit more time goes by, but it's really difficult to draw conclusions on what may or may have occurred in a one quarter period.

Mohit Bansal - Wells Fargo - Analyst

Got it.

Leonard Schleifer - President and Chief Executive Officer

There's still here's still quite a bit of room of growth in the diabetic guide diseases area where we still see a decent growth there in that category.

Mohit Bansal - Wells Fargo - Analyst

Helpful, really. Thank you.

Ryan Crowe - Vice President, Investor Relations

Thank you, Len and Marion and Mohit. Next question please, Tawanda.

Operator

Thank you. Please standby for your next question. Our next question comes from the line of Christopher Raymond with Piper Sandler. Your line is open.

Christopher Raymond - Piper Sandler - Analyst

Hey, thanks. Just another question maybe on the VEGF market and EYLEA specifically. So in our checks, we get a sense that there's some docs who believe that providers [Phonetic] will confers differentiated efficacy, but on the other hand, there's still a sizable amount of docs who've yet to see a patient for follow-up after the first dose. Sort of just curious if in the field, you're seeing a difference in perception of the by now by time of experience. That is any discernible change in perception of the more patient follow-up they've had? Thanks.

Marion McCourt - Executive Vice President, Head of Commercial

I think it's probably best that Rose answer questions on what they're hearing about use. I'll just share at this point, I haven't heard characterization of that. Use is still at a low level, in fact, quite modest. I can characterize the EYLEA performance as I did in terms of market leadership and the growth we see in our business in terms of market share and other parameters. And that is across indications and certainly substantially creating EYLEA as leader in the anti-VEGF category. And obviously, we're very enthusiastic as is the retina community, probably even more important about the possibilities and potential of aflipercept 8-milligram, if approved in the future.

Ryan Crowe - Vice President, Investor Relations

Thank you, Marion. Next question, please.

Operator

Please standby for our next question. Our next question comes from the line of Colin Bristow with UBS. Your line is open.

Colin Bristow - UBS - Analyst

Hey, good morning, and congrats on the quarter. So on EYLEA in '23, was starting to see some formulary updates. So I was wondering could you just speak to how you see the market share evolving over the quarter '23 in light of the Bizmo [Phonetic] and then obviously biosimilars? And then just as we think about high-dose value in the back half of the year, anything you can say in terms of anticipated opex changes? Thank you.

Marion McCourt - Executive Vice President, Head of Commercial

So as a start, we don't predict future market share performance. So I'm going to stay away from specifics in that area. Certainly, not only this quarter, but over several quarters, we've been able to demonstrate continuing strong performance with EYLEA as anti-VEGF category leader, and certainly, we'll continue to work on that. And as agents have entered the market, our competitive readiness abilities have been very strong. But most important, frankly, it's the profile of EYLEA, the clinical attributes, the safety of the product, the breadth of indications, ease of access for physicians and patients.

But going forward, certainly, we'll be very much prepared to launch aflibercept 8-milligram. And as we get into that launch potentially with an FDA approval, we'll be able to give more characterization, but as George and Len described today, the profile we see with aflibercept 8-milligram and opinion leaders in the retina community confirm that this profile potentially has all the ingredients to become standard of care. And certainly, that's what we'll work on all the benefits of vision, coupled with safety and now this potential of substantial durability that hasn't been seen before in the category.

Robert Landry - Executive Vice President and Chief Financial Officer

Colin, it's Bob. With regards to opex, I mean, Marion and I will do what we always do on the brands. We'll look at what totally makes sense. I mean, as you know, it's kind of a defined number of retinal docs. So it's not as if we're going into a tremendously new area that creates a lot of new touch points on it. And on top of that, Marion's team right now is a very tight-functioning sales rep team on the top of their game. So again, we don't expect some gigantic pivots in this area. But again, we will make sure that we fund this appropriately and that it is - the commercial side of it is going to match how well the clinical data is going to stand up on it. Thanks.

Colin Bristow - UBS - Analyst

Thank you.

Ryan Crowe - Vice President, Investor Relations

Okay. Next question next question, please.

Operator

Thank you. Please standby for our next question. Our next question comes from the line of Brian Abrahams with RBC. Your line is open.

Brian Abrahams - RBC Capital Markets - Analyst

Hey, good morning. Thanks for taking my question, and congrats on the continued execution and innovation. On the prostate bispecific, now that you've had more time with the evolving data, any views on predictors of response or durability there? And I'm curious how your learnings might shape your latest thoughts on threading the therapeutic window, both for the PSMA as you accelerate the trial enrollment as well as your other costimulatory bispecifics. Thanks.

George Yancopoulos - President and Chief Scientific Officer

Yeah, I think that our data actually shows that with the remarkable response rates we saw, especially going to the higher doses that it's not as if you have to look hard to find biomarkers for response. Remember, just to remind you that at the highest dose, three out of the four patients had very profound responses. So response predictors are not necessarily the issue, but you also point to the question about therapeutic window. Certainly, we are seeing autoimmune-related side effects associated with these responses.

And so we are working hard now. We are actually - we've accelerated enrollment in this program. We're trying to understand more the relationship between the responders and having these autoimmune side effects. I mean, one, very positive perspective is we don't see these serious autoimmune side effects and people who don't see responses. So it's the people who benefit who do get the autoimmune side effects. These are obviously coupled. It's because I think the drug is doing what we intended to do. I think this is some of the most exciting data in the history of immunotherapy that you can take where people have historically called a cold tumor that has almost no responses to immunotherapy or the PD1 therapy and get these incredibly high rates of very deep and so far durable responses. And we will continue to work on improving the therapeutic window.

In terms of the bispecific program more broadly, and I want to harken back, Len sort of answered the previous question about CD20 and BCMA. But I do want to amplify on some of those comments, which is, we think that there are indeed a very small number of bispecs in the CD20 space and the BCMA space, which are actually looking quite competitive with each other, including ours. So the emerging data suggests the efficacy and safety profiles of these agents will be competitive with each other. We'll see our updated data we'll present it at ASH. But I think what's emerging is that these small numbers of competitors will exist in this field. I think that there's going to be room for these. There's actually a lot of patients in these late-stage settings who need treatment. So I think that there's going to be room for these small numbers of competitors there.

But the future is going to be about moving into earlier lines of therapy, and there's going to be subtleties there about how one executes, designs those studies, the co-therapies, more standard co-therapies that are used there. And so there's going to be a lot of actually art to how one moves these agents into the earlier lines of therapies. But the other very important thing is in addition to moving into earlier lines of therapy with these more standard combinations where, as I said, there's going to be a lot of art to doing those studies is going to be the of novel combos.

And as we just talked about with the CD20 and costim bispecifics that we've now shown that we're leading the field with in prostate cancer. We have very similar type agents now that we're going to be combining with our CD20 bispecific in lymphoma and with our BCMA bispecific in myeloma. And we think that these are going to really have the opportunity to continue to change the game and change the practice of medicine for these patients.

So it's about taking agents that are indeed going to be competitive and quite competitive with each other in these late-stage settings where I think they're all going to be making important contributions to the treatment of these patients, but then moving in very artful ways to these earlier lines of therapy and using them there, where I think there's also going to be room, but there's always going to be room for differentiation as well as the future. We are making these combos with all of these exciting opportunities we have in our portfolio, can really take the utilization of these agents and the treatment for these patients and these cancers to a whole another level, as we believe we're already showing that we're doing in prostate cancer.

Leonard Schleifer - President and Chief Executive Officer

George, there was one question about biomarkers in prostate cancer. Maybe you might just comment on how quickly you can use PSA in studies after people were exposed to both agents.

George Yancopoulos - President and Chief Scientific Officer

Right. And some of the data we've already shown and we will continue to show many of our patients have remarkably high PSA levels because they have very high burden of disease, as we all know, depending on the assay and the labs and so forth, normal PSA levels are in the single to low-single digits, maybe one to four is considered the highest levels. We have patients who entered into our study with PSAs in the hundreds, 500, 600 and so forth.

And we saw with this combination treatment as soon as you put the combination onboard, essentially at the next time point that we measured within three weeks or so, we saw a dramatic drop on the order of 99% reductions in the PSA. And these are really astounding results. And now where we continue to follow up patients over time. We've seen that, for example, bone lesions have entirely normalized and so forth. So the effects are incredibly rapid as reflected in the PSA.

And to the point about predicting which patients respond, it doesn't matter whether you had patients who had relatively low burden as measured by PSA, where their PSA was measured in the - in, let's say, 40% to 50% range or whether you had incredibly high PSAs in the 500 to 600 range, those patients seem to similarly respond in terms of very dramatic, very profound drops in the PSA within weeks of starting therapy.

And as we've continued to follow these patients, incredibly durable responses are first patient has now been out for more than a year. Their immune side effects have resolved, whereas their complete remission has remained completely intact. And as I said, not only completely normalize the PSA levels, but the bone lesions and so forth have all normalized, at least as measured by bone scans and so forth. So this is really - has the potential to be so game-changing for these late-stage patients who really have at this point, no other real recourse.

Ryan Crowe - Vice President, Investor Relations

Thank you, Len and George. I think we have time for one more question, Towanda.

Operator

Thank you. Please standby for our final question. Our final question comes from the line of Carter Gould with Barclays. Your line is open.

Carter Gould - Barclays - Analyst

Good morning. Thanks for taking - squeezing me in and taking the time. Maybe just to come back to - for Marion, just how we should think about your expectations for the time line to receive a J-code for high-dose EYLEA next year. We've seen in the past pretty varied time lines here in terms of Libtayo there has turned around almost immediately Roche clearly had a more paced process. And I guess more to the point, should our expectation be that's more of like a January 1, 2024, type event? Or is the potential for a J-code maybe in the later part of '23? Thank you.

Marion McCourt - Executive Vice President, Head of Commercial

Carter, thank you for the question. And certainly, we'll stay very close on this. And obviously, the importance of new BLA, new J-code is important. In terms of timing, I would need a crystal ball. Certainly, we'd share with you. We'll be working very closely with the proper organizations and officials. But at this time, it's too early to give anything definitive on expectation for J-code timing.

Leonard Schleifer - President and Chief Executive Officer

Yeah. And this in Len, I mean my own perspective, I'm just slightly different is that I'm not convinced in this particular setting that the J-code is like the end of deal of - like you're going to see these dramatic changes in uptakes post J-code.

Carter Gould - Barclays - Analyst

Thank you.

Ryan Crowe - Vice President, Investor Relations

Okay. I think that's all we have time for today. Thank you, everyone, for joining the call. As always, the Investor Relation is standing by for any follow-up questions you may have. Have a great day, everyone.

Operator

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REGENERON PHARMACEUTICALS INC

Q3 2022

Earnings Transcript

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