Ian Haydock (00:09):
Hello and welcome to the podcast version of Scrip’s Five Must-know Things. This time for thebusiness week ended June 30th, 2023. This is Ian Haydock.
This time ―Lilly wows ADA with obesity results; Novo’s oral semaglutide data, first DMD genetherapy approved; the outlook for biopharma fundraising; and Korean pharma considers
strategy in a changing world.
Eli Lilly is a few years behind Novo Nordisk in bringing a GLP-1 agonist to market for obesity, butit presented data at the American Diabetes Association or annual meeting that could give thecompany a best-in-class portfolio of medicines, including its GLP-1/GIP/glucagon (GGG)
receptor tri-agonist retatrutide, which generated weight loss of up to 24.2% in overweight andobese patients without diabetes at 48 weeks. In a Phase II clinical trial presented on June 26.
[Scrips’] Mandy Jackson writes that Novo Nordisk already market the injectable GLP-1 agonist
Wegovy for obesity in the US and plans to submit the high-dose oral version of semaglutide for
US and EU approvals this year based on the Phase III OASIS 1 trial presented on June 25 at ADA
in San Diego.
(01:32):
Lilly’s injectable GLP-1 GIP agonist Mounjaro™, which the US FDA approved for type 2 diabetes
in 2022 could win US approval for obesity by the end of 2023, providing the company's firstentry to the US obesity market and offering a formidable competitor for Wegovy.
Lilly's slate of obesity data at ADA included Phase III results for Mounjaro in overweight andobese patients with type 2 diabetes, as well as Phase II results in non-diabetic individuals whoare overweight and obese for tirzepatide as well as for orforglipron, an oral non-peptide GLP-1agonist. The latitude drugs have moved into Phase III development ― orforglipron for both type2 diabetes and obesity, and tirzepatide or chronic weight management.
“Right now our belief is we have the broadest portfolio of type 2 diabetes and obesity
treatments in various phases of development across the industry,” Jeff Emek, who's senior vicepresident of product development at Lilly Diabetes, said in an interview at ADA.
Across GLP-1 agonists obesity presentations at ADA, including for Lilly’s and other companies’
drugs, experts noted that weight loss tends to be observed at higher levels in obese andoverweight patients who do not have diabetes than in trials where patients’ comorbidities
include diabetes. For Mounjaro, Lilly reported weight loss of 21.4% for the 10-milligram, onceweekly dose of the drug and 22.5% for the 15-milligram dose at 72 weeks in the Phase III
SURMOUNT-1 trial at ADA in 2022.
Staying with ADA, Mandy also writes that the race to bring an oral obesity agent to market isheating up. Novo Nordisk presented detailed results for the oral version of its GLP-1 agonist
semaglutide on June 25 at the meeting from the Phase IIIa OASIS 1 clinical trial with 15.1%
mean weight loss observed in overweight and obese adults versus 2.4% for placebo, confirming
topline results released in May.
The readout took place two days after the presentation of Phase II data at ADA for Lilly’s oral
GLP-1 drug orforglipron, which could be a formidable competitor. Overweight and obese adults
treated with the highest dose of orforglipron achieved weight loss of 14.7% at 36 weeks in
Lilly's phase two study, and the weight reductions did not plateau before the end of the 36week trial. Both Novo’s OASIS 1 trial and Lilly's phase two trial recruited overweight and obese
adults with at least one comorbidity excluding type two diabetes.
While Novo plans to submit its once-daily all or semaglutide 50-milligram dose for US and EU
approvals as a treatment for obesity in 2023, the company has not committed to specific filingor launch timelines, which are dependent on Novo's capacity to supply its US-approved
injectable version of semaglutide, Wegovy.
(04:46):
While Wegovy has had an impressive obesity launch that is injectable GLP-1/GIP agonist,Mounjaro, cleared by the FDA for type two diabetes in 2022, could be approved in the US by
the end of 2023, based on the Phase III SURMOUNT-1 and SURMOUNT-2 trials. Detailed resultsfrom SURMOUNT-2, which enrolled overweight and obese patients with type 2 diabetes, werepresented at ADA, showing mean weight loss of 13.4% for the 10-milligram weekly dose and15.7% for the 15-milligram weekly dose at 72 weeks.
Besides orforglipron, a third oral GLP-1 competitor also is close behind oral semaglutide and
Lilly’s drug, since Pfizer has two GLP-1 drugs in Phase II, with data expected later in 2023 andearly in 2024, which will inform the company's decision about whether to move its once-dailyor twice-daily molecule into Phase III.
(05:48):
Sarepta Therapeutics is confident its newly approved gene therapy for Duchenne muscular
dystrophy or DMD, Elevidys, will be a commercial despite initial age restrictions and carrying aprice tag of $3.2 million. The company has worked at being transparent around pricing andbelieves “the work that we've done to support the pricing of this therapy is potentially a
blueprint for others,” CEO Doug Ingram said during a June 22nd analyst call about the approval.
Jessica Merrill and Mary Jo Laffler, write that the US FDA, granted an accelerated approval to
Sarepta's gene therapy, although the approval is for a narrow indication in children 4 to 5 years
old and is based on a surrogate endpoint expression of dystrophin protein, rather than a clinicalendpoint.
Wholesale acquisition costs for the gene therapy is $3.2 million, although “nearly all infusions

will be subject to a statutory discount for Medicaid or 340B discounts, so with distribution andother discounts, you should be modeling a gross to net adjustment in the mid-20% range.,
Ingram told the call.
The price tag is well below what the company could have tried to justify. On May 26, it
published an article in the Journal of Market Access & Health Policy using an establishedpharmacoeconomic model, which concluded that as a one-time treatment Elevidys is costeffective at a price of $5 million to $13 million.
While the company said it's “ready to serve the market today,” there are some steps that haveto happen before a patient is dosed, including securing reimbursement agreements withpayers. Ingram cautioned that the ramp up will be slow, similar to that seen for Sarepta's earlier
DMD products, Exondys, Amondys and Vyondys, due to the size of the population and theadditional gene therapy steps,” such as screening for neutralizing antibodies, site procurement,and post-therapy monitoring.
Sarepta is the first company to gain approval for a DMD gene therapy, beating others to themarket, including Pfizer, which has a Phase III candidate. While questions remain about
Elevidys’s long-term safety and efficacy with a Phase III study still ongoing, the approval
nevertheless marks an important milestone in the effort to develop a cure for DMD.
Biopharmaceutical investors and executives alike conceded during the recent international
convention that the booming financial environment, which peaked in 2020 and 2021 withrecord levels of venture capital investment and initial public offerings, created too many new
drug development startups and public companies.
Many therapeutics firms shut down as investment in the sector slowed in 2022 and early 2023
― a trend that is likely to continue ― but to others have adjusted to the new market realities.
Mandy Jackson spoke with several investors and executives at BIO about their expectations forwhen this downturn in the financial market will turn around, but none had a clear view of when
the industry could expect a significant change. Speakers on June 5th panel titled “Biopharma
Dealmaking in Uncertain Times” also offered advice for keeping companies afloat until themarket cycle reverses course ― whenever that might happen.
Venture capital firms are investing more conservatively to preserve their existing funds for only
the highest-quality startups and to back companies they funded previously. Since the IPO
market largely shut down in 2022, VC investors have had to finance their portfolio companies
through series B, C or later rounds to keep research and development programs going. Andwith fewer companies exiting their portfolios via IPOs and too few leaving via acquisitions,many VC firms are enabled to raise new funds.
Chris Garabedian, who's chairman and CEO of the biotech accelerator and investment firm
Xontogeny, explained to Scrip that this has set up a musical-chairs scenario in the VC arena. VC

investors go out looking for other firms to join syndicates to back funding rounds for theirportfolio companies, but their peers turn down those opportunities and at the same time ask
for participation in financings for their own portfolio companies.
(10:16):
Garabedian further noted that VC firms typically have a five- to 10-year investment period fortheir funds, but firms were investing their money more rapidly during the exuberant
investment cycle before 2022 and then quickly going out to raise new funds. “Now, every VC I
know is going to be taking full advantage of that investment,” he said. “That means the bar isgoing to get raised higher because you're going to say ‘no’ to things you would've said ‘yes’ to acouple of years ago.”
On the public company side, EY senior advisor Barbara Ryan noted during the same dealmaking
panel that broader macroeconomic concerns ― such as rising inflation and increased interest
rates, plus the uncertainty of whether the US and other global economies are entering arecession ― have caused investors to shift their money from high-risk sectors such as
biopharma to lower-risk investments. That will change, but, in the meantime, themacroeconomic climate will be a major headwind for biopharma firms, Ryan said.
Amit Mehta, who's vice president and head of business development for Genentech Researchand Early Development, noted that biotech firms, when they're seeking financing, whether it's
through the public markets or through the private markets, the focus is on ensuring that they
have a truly differentiated platform or asset.
(11:37):
Finally, amid a weak global economy and big pharma cutbacks and less aggressive dealmaking,Korean biopharma firms looking to enter global markets should also adopt different strategies,
according to one prominent executive in the country, Jung Won Shin writes.
Korean Drug Development fund CEO H. Samuel Muk shared his views in a recent webinarorganized by EBN, noting: “They can't survive with the same strategies in a time of economic
slump; ‘select and focus’ becomes a truth in the end.”
He suggested several business models according to the types of biopharma players in Korea,
the first being a contract manufacturing organization model. As this may require investments ofbillions of dollars in production facilities, it's more suited for large firms such as conglomerates.
The second model is based on using new drugs to enter major markets, something Muk viewed
as appropriate for Korea's top five mainstream pharma firms.
Thirdly, next year, companies with annual sales of around 500 billion Korean, such as Dong-AST, an affiliate of Dong-A Socio Holdings and Ildong Pharmaceutical Co., Ltd., cannot invest
substantial amounts in R&D because of their limited size. As a result, their strategy will need toinvolve the creation of new drug development subsidiaries that could attract funding fromventure capital sources.
The fourth viable strategy for Korean firms would be to pursue continuous out-licensing deals,
something that could apply largely to many biotechs listed on the Kosdaq market, which areunable to complete late clinical development and commercialization by themselves. Thisapproach is predicated on a steady flow of pipeline assets to be partnered at the middevelopment stage.
(13:24):
Finally, the “pharmerging” model involves entry into large-population markets such as
Southeast Asia, South Asia, the Middle East, and central South America, something that Korean
firms like Korea United Pharm and Boryung could do with incrementally modified products viajoint ventures and co-research deals.
Furthermore, an IPO should not be the only strategy for a bio venture, which needs to think
about a sustainable business model after this to feed the R&D pipeline, generate out-licensing
deals and operating profit, and find partners for global markets. In addition, firms need to getbigger through mergers with companies with similar business models to reduce costs, hesuggested.
That's all for this time. Many thanks for listening. These stories form just a fraction of Scrip’s
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Note: This transcript was generated with the use of AI.