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Thursday, July 18, 2019

Genmab Raises $506 Million in IPO

Genmab A/S, located in Copenhagen, Denmark, raised $506 million with its initial public offering (IPO). The company trades on the Nasdaq under the ticker symbol GMAB.
The company’s ordinary shares are currently listed on Nasdaq Copenhagen under the GEN symbol. Each American Depository Share (ADS) represents the right to one-tenth of an ordinary share. The Genmab shares are listed on the Nasdaq Copenhagen and the ADSs on the OTC market in the U.S.
The company was founded in 1998 and reported $440 million in sales for the 12 months ending March 31, 2019. The company’s portfolio includes two marketed drugs developed with partners. The first is Darzalex (daratumumab), a human CD38 monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) for multiple myeloma. It was developed and marketed with Johnson & Johnson’s Janssen Biotech.
The second commercial product is Arzerra (ofatumumab), developed and marketed with Novartis, for specific indications of chronic lymphocytic leukemia.
“Our vision is to transform cancer treatment by launching our own proprietary product by 2025 and advancing our pipeline of differentiated and well-tolerated antibodies,” the company stated in the SEC filing.
That pipeline includes five product candidates in clinical development and about 20 proprietary and partnered preclinical programs, including two of its internal product candidates. Genmab has either submitted or plans to submit an IND to the FDA or a clinical trial application (CTA) to the European Medicines Agency (EMA) this year for these candidates.
The company dosed its first patient in a Phase I/II clinical trial in May 2018 for HexaBody-DR5/DR5 and DuoBody-CD3xCD20 in a Phase I/II trial for B-cell malignancies in July 2018.

Genmab also has a proprietary candidate Enapotamab vedotin (HuMax-AXL-ADC) in Phase I/II development for multiple solid tumors including ovarian, cervical, endometrial, thyroid, non-small cell lung cancer, melanoma and sarcoma. It is an antibody-drug conjugate (ADC) that targets Axl and uses technology licensed from Seattle Genetics. An ADC is an antibody for a specific target that is attached by molecular linker to a chemotherapy drug. It allows for more specific delivery of the toxic chemical.
Seattle Genetics is also a development partner with Genmab for tisotumab vedotin, currently in Phase II in cervical cancer, ovarian cancer, and solid cancers. It is an ADC targeted to tissue factor (TF), which is involved in tumor signaling and angiogenesis.
The company also has partnerships with ADC Therapeutics, BioNTech, Bristol-Myers Squibb, Lundbeck, and Horizon Pharma.
Darzalex brought in $90 million in milestone payments, so-called “bio-bucks,” and $262 million in royalties in 2018, which made up almost 76% of Genmab’s revenue last year. It is being evaluated in numerous clinical trials in hopes of expanding its use. However, it is likely to face competition in the near-future from Sanofi and its isatuximab, which is being reviewed by the FDA and the EMA.
In 2018, Genmab’s total revenues rose 28% to $455.28 million with 33% net profit growth to $221.55 million. In the first quarter of this year, revenues and net profit dropped 13% and 64%, respectively, hitting $88.95 million and $10.87 million.
Genmab’s other marketed product is Arzerra, partnered with Novartis. This drug hasn’t quite caught on, with Novartis reporting net sales of $26 million last year, creating about $5 million in royalties for Genmab. It has been approved for chronic lymphocytic leukemia and is being evaluated for multiple sclerosis.

Novartis needs new launches to keep up momentum

A strong second quarter pushed Novartis’s stock up 5% this morning, but Kymriah continues to look weak, and the jury is still out on Zolgensma.
Novartis’s rebranding as an innovative drug company is picking up steam. But the group’s CAR-T therapy Kymriah still looks like it will fall short of already modest expectations this year – and a discontinuation in chronic lymphocytic leukaemia will not help the group’s blockbuster ambitions.
And Novartis would not give concrete details on its big new launch, the spinal muscular atrophy gene therapy Zolgensma, despite being pressed repeatedly on a conference call today. The company will need these therapies, as well as other new products like Mayzent and Piqray, to do well if it wants to keep up the current momentum.
Still, a strong showing in the second quarter of 2019, when Novartis beat sales and earnings expectations and raised full-year 2019 guidance, moved the company’s stock up 5% this morning.
True, expectations were probably not high for Kymriah, which has been a commercial disappointment since its launch in 2017. Second-quarter sales of $58m were up 263%, but from a very low base, and at current rates the product will have problems hitting the already reduced EvaluatePharma sellside consensus of $237m this year.
The discontinuation in chronic lymphocytic leukaemia (CLL) could be another blow, but in reality getting a foothold in this disease, which is already well served, was always going to be a hard task for CAR-T. There are worries about whether CAR-T would be too harsh for CLL, which generally progresses slowly, and whether its cost would be justified in what is a relatively old patient population.
Novartis had not responded to questions about the reasons behind the CLL discontinuation at the time of publication, but if the decision was indeed down to concerns about CAR-T’s competitiveness it could be bad news for JCAR017. Celgene increased the CLL focus for the Juno-originated project last year, but it is unclear whether JCAR017’s soon-to-be new owner, Bristol-Myers Squibb, has similar plans (Ash 2018 – The JCAR017 development path takes another twist, December 2, 2018).
A look at other CD19-targeting CAR-T assets shows several in development in CLL, but many ongoing trials involve academic institutions.
ONGOING WESTERN TRIALS OF CD19-TARGETING CAR-T PROJECTS IN CLL
ProjectTrial detailsSponsorTrial IDPrimary completion
3rd-gen CD19 CAR-TB-cell malignanciesUppsala UniversityNCT03068416Apr 2019
KymriahImbruvica combo in r/r CLL or SLLUniversity of PennsylvaniaNCT02640209Oct 2019
CD19 CAR-TSagan; advanced B-Cell NHL, ALL, and CLLBaylor College of MedicineNCT01853631Dec 2019
“Armored” CD19 CAR TCLLMemorial Sloan Kettering/JunoNCT03085173Mar 2020
3rd-gen CD19 CAR-TCLL, ALL, DLBCL, follicular lymphoma, mantle cell lymphomaUniversity Hospital HeidelbergNCT03676504Mar 2020
MB-CART19.1CLL, ALL, B-cell lymphomaMiltenyi BiotecNCT03853616Jul 2020
JCAR017With/without Imbruvica in r/r CLL or SLLJuno/CelgeneNCT03331198Dec 2020
KTE-X19Zuma-8; r/r CLLKite/GileadNCT03624036Mar 2021
CD19/CD22 CAR-TALL, B-cell leukaemia/lymphoma, NHLNCINCT03448393Dec 2021
CD19 CAR-TCLL, ALL, NHL, acute biphenotypic leukaemia, SLLMD Anderson Cancer Center/NCINCT02529813Dec 2021
CD19/CD20 CAR-TCLL or B-cell lymphomaJonsson Comprehensive Cancer Center/NCINCT04007029Aug 2022
KymriahWith/without Imbruvica in CLL/SLL and DLBCLNovartisNCT03960840Dec 2022
CD19 CAR-TCLL, NHL, ALLFred Hutchinson Cancer Research Center/NCINCT01865617Apr 2029
Source: Clinicaltrials.gov.
Zolgensma is more important for Novartis now. The company said today that the launch was going well since the gene therapy’s US approval in May, but details were thin on the ground.
Novartis will provide sales data in the third quarter for Zolgensma, as well as for another recent launch, the multiple sclerosis therapy Mayzent.
Investors might have to wait even longer to get figures on the breast cancer therapy Piqray, whose uptake will depend on PIK3CA mutation testing – and Novartis said that boosting uptake of the test would be its focus this year.
LIVING UP TO EXPECTATIONS? SELECTED NOVARTIS RECENT LAUNCHES
ProductIndicationApproval date2024e sales ($m)
KymriahPaediatric ALL, DLBCLAug 20171,009
MayzentMultiple sclerosisMar 20191,312
PiqrayHR+/Her2- breast cancer with PIK3CA mutationMay 2019821
ZolgensmaSpinal muscular atrophyMay 20191,569
Source: EvaluatePharma.
As for future readouts, all eyes are on the Paragon trial of Entresto in heart failure patients with preserved ejection fraction, slated to be presented as a late-breaker at September’s European Society of Cardiology meeting in Paris.
Despite having had its abstract accepted, Novartis said this was merely a placeholder and it had not yet seen any of the Paragon data. The company believes that it can succeed where others have failed by looking at first as well as recurrent hospitalisations, but investors face a nervous wait (Upcoming events – Novartis and Miragen hope for heartening data, June 21, 2019).
The MS project ofatumumab and the asthma candidate fevipiprant will also yield pivotal data later this year. Novartis has a packed pipeline, a luxury that many other big pharma players cannot claim, but it needs to deliver.

FDA OKs Novartis’ generic Farxiga

The FDA tentatively approves Novartis (NVS +3.6%) unit Sandoz’s marketing application for a generic version of AstraZeneca’s (AZN +0.4%) type 2 diabetes med Farxiga (dapagliflozin).
Tentative approval means that the application met the criteria for approval but patent issues need to be resolved before the the agency grants full approval.
Farxiga generated ~6% of the company’s Q1 product sales ($349M/5,465M).

Fulcrum Therapeutics Opens Below IPO Price

Fulcrum Therapeutics, Inc. NASDAQFULC made its public debut on Thursday morning, opening at $14.50 after being priced at $16 per share.
Fulcrum focuses on developing therapies for genetically defined diseases in areas of high unmet needs, with a specific focus on rare diseases. The company uses its product engine to identify targets that can be drugged by small molecules, regardless of the particular underlying mechanism of gene misexpression.
Morgan Stanley, Bank of America Merrill Lynch and SVB Leerink are the underwriters for the offering.
The stock traded around $14.36 per share at time of publication.

Still on a cash-raising spree, Takeda shops €1.5B European drug sale

Takeda’s ax is about to fall again, this time on some over-the-counter and off-patent prescription drugs in Western Europe.
The Japanese pharma, still working to pay down debt it incurred for its Shire buy, tapped J.P.Morgan to help it find a buyer—or buyers—for some European consumer and prescription drugs, Reuters reported, citing sources close to the matter.
It hopes to fetch around €1.5 billion ($1.68 billion) for the products, most of which have already lost patent protection, the newswire said.
Who might step up to bid? Private equity funds interested in healthcare, European biopharma players and Indian or Asian drugmakers looking to expand in Europe, Reuters’ sources said. For instance, the German drugmaker Stada and its backers Cinven and Bain Capital; Italy’s Recordati and its investor CVC Capital Partners; and Zentiva, which Sanofi sold to Advent International last year.
But Takeda could have competition for those bidders: They’re among those who could snatch up some European OTC products from the new GlaxoSmithKline-Pfizer joint venture, Reuters recently reported.

The sale comes as Takeda continues to jettison noncore products to help pay off the debt built up during its $60 billion Shire buyout. The Japanese drugmaker has said it wants to cut $10 billion worth of assets outside its five priority business areas, namely gastroenterology, rare diseases, plasma-derived therapies, oncology and neuroscience.
Takeda already sold Shire’s dry eye drug Xiidra to Novartis in a deal potentially worth $5.3 billion, and handed Johnson & Johnson its TachoSil surgical patch. It’s also close to finalizing a buyer for its $1 billion Latin American business. Brazil’s largest drugmaker, EMS, is the frontrunner for that deal, and Reckitt Benckiser and Uruguay’s Megalabs are also on the shortlist, Reuters’ sources said.
Besides portfolio selloffs, Takeda is rearranging on the real estate side. Its old U.S. headquarters in Deerfield, Illinois, for instance, will retire by Dec. 31. The company is moving about 1,000 employees to its new U.S. operations in the Boston area, and it’s expected to put the Deerfield facility up for sale by March next year.

J&J: DRC rejects clinical trial for experimental Ebola vaccine

An experimental vaccine intended to combat the Ebola outbreak in the Democratic Republic of the Congo (DRC) has now been rejected for use.
Dr Oly Ilunga, health minister for the DRC, previously suggested clinical trials of the Johnson & Johnson vaccine could be held in the country, although not in the outbreak zone where Merck’s experimental vaccine is being used.
In late June, Ilunga said that the DRC would consider approving applications for vaccine trials on the condition that Congolese scientists were involved and the vaccines were tested in other parts of the country, rather than near the Ebola outbreaks.
However, there were concerns over the logistical challenges posed by the Johnson & Johnson vaccine, which is designed to prevent outbreaks, rather than stop them. The vaccine is delivered in two doses administered almost two months apart, presenting logistical problems, especially among communities that travel and have no identity cards.
“We are in a very critical outbreak in a very complex environment,” Ilunga said. “We want to have all the human resources dedicated to the outbreak. We don’t want people to be diverted in another clinical trial elsewhere in the country.”
The Merck vaccine has been administered to almost 162,000 patients since last August.
Johnson & Johnson has stated that it remains poised to mobilise its vaccination efforts in the country if called upon.

Gilead: New Data on HIV Prevention, Treatment, Cure at AIDS Society Meet

Gilead Sciences, Inc. (NASDAQ: GILD) today announced that new data from the company’s HIV research and development programs will be presented at the 10thInternational AIDS Society Conference on HIV Science (IAS 2019) being held in Mexico City from July 21-24. Fifteen abstracts, along with community-focused symposia and workshops, reflect Gilead’s ongoing commitment to scientific innovation, a key pillar to addressing unmet and evolving medical needs in HIV.
“Gilead’s scientific discovery has helped transform both HIV treatment and prevention and we are committed to advancing the next generation of therapies to improve the care of people and communities impacted by this disease,” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research & Development, Gilead Sciences. “Our data at this year’s meeting include exciting progress in our HIV prevention, treatment and cure programs, which together are helping to advance the field of HIV toward the ultimate goal of ending the epidemic.”