Pfizer selloff enhancing attractiveness

Pfizer (PFE -7.2%) investors heading for the exits after disappointing results from an Ibrance (palbociclib) study should reconsider says the Wall Street Journal.

Shares have been under water today since the company announced that the study, testing the effect of the kinase inhibitor over and above endocrine therapy in early-stage HR+/HER2- breast cancer patients, is unlikely to achieve the primary endpoint of extending survival.

The paper says the setback, potentially dimming hopes of billions in extra revenue, is not catastrophic considering the company’s size, adding that Ibrance currently generates ~$5B in sales in the HR+/HER2- breast cancer population and some oncologists are already prescribing it off-label as adjuvant therapy. Sales jumped 10% in the past quarter from a year ago and key patents remain in effect until at least 2023.

The company’s shares are well-supported at 12x 2020 non-GAAP EPS guidance with a healthy 4% dividend yield.

https://seekingalpha.com/news/3579178-pfizer-selloff-enhancing-attractiveness-wsj

UK public fears cyber-attacks with COVID-19 tracing app

Almost half (48%) of people in the UK questioned about the NHSX contact-tracing app say they don’t trust the government to keep their information safe from hackers, according to a 1,000-person survey.
The smartphone app, which is being piloted on the Isle of Wight, is part of the government’s ‘test, track and trace’ strategy as the country eases out of coronavirus lockdown, with fewer restrictions in social distancing starting from today.
The poll – conducted by Censuswide for cyber-security company Anomali – also found that 43% of respondents were worried that using the app would give fraudsters the opportunity to launch phishing attacks by email or SMS.
Moreover, just over half (52%) of people felt they were savvy enough to differentiate between a legitimate email or text message and fraud attempt.
For now at least it’s something of a moot point, as the UK’s track and trace approach is relying on conventional means, with 25,000 contact tracers using phone and email to warn those exposed to people contracting the virus to self-isolate.
There are also reports that the app is having teething problems that could delay its national roll-out, although NHSX is said to be working on a second-generation version to overcome the problems. The latest government line is that it will be available nationally within a few weeks.
Nevertheless, concern about the safety of the app amongst the general population could have a big impact on how willing people are to install it on their phones, and if too few do so it will be rendered ineffective.
The Censuswide survey also revealed that more than a third (36%) of people are also concerned that the app could be used by the government to collect data on them.
“At this stage, nobody knows where to get the NHSX app from, so it can be reasonably expected that consumers will be faced with floods of emails with bogus links to convincing looking domains to download the app from,” says Anomali’s Jamie Stone.
There have already been cases reported in the UK in which fraudsters have sent text messages to people to try to fool them into believing they have been in contact with someone who has tested positive for coronavirus, and directing them to a website that seeks to harvest their personal details.
Stone thinks this form of attack is more dangerous than phishing emails, as “due to the smaller screen real estate, people will be less able to check the veracity of the link so will be more trusting and might click it.”
“We’re already seeing thousands of rogue and spoof COVID-19 domains being registered and used in attacks,” he adds.

Survey says UK public fears cyber-attacks with COVID-19 tracing app

Gilead trumpets data with newly-bought magrolimab in blood cancers

Just three months after acquiring Forty Seven for $4.9 billion, Gilead has reported positive data on magrolimab, the lead drug from the deal, at ASCO 2020.
Phase 1b data presented at the congress showed that the combination of the CD47-targeting antibody with azacitidine achieved a 91% overall response rate (ORR), with 42% complete responses, in patients with previously-untreated myelodysplastic syndrome (MDS).
After a minimum of six months of follow-up, the complete response rate had grown to 56%, suggesting the effect was durable and improved over time.
The study also tested the combination in acute myeloid leukaemia (AML), with an ORR of 64%, 56% of which were complete responses. The AML arm was carried out in patients who weren’t strong enough to tolerate the intensive chemotherapy that would be the usual first-line treatment option.
12 out of 29 patients in the AML group had TP53 mutations, which are associated with a particularly poor prognosis, and eight (75%) of them achieve a complete response with the combination.
The 68-patient study is small but the high response rate reinforces the potential of CD47 as a therapeutic target in cancer. It’s described as a ‘don’t eat me’ signal given off by cancer cells to evade destruction by while blood cells called macrophages.
Some studies have also suggested that blocking CD47 can also push malignant cells into a form of suicide known as apoptosis.
The strong data signal now has Gilead debating whether the single phase 1b trial could be enough to file for accelerated approval with the FDA using regulatory pathways that allow early access to promising new therapies for cancers with few treatment options. It eventually aims to enrol around 257 subjects into the study, which is still ongoing.
The company says it intends to discuss that with the FDA, while also moving ahead with additional trials of magrolimab in MDS and TP53-mutant AML.
When Gilead acquired Forty Seven in March, chief executive Daniel O’Day said the deal would complement a pipeline of cell therapies for blood cancers from Kite Pharma, which the company bought for $11.9 billion in 2017.
Approximately 15,000 people are diagnosed with MDS in the US each year, with no new treatments approved in 14 years, and there are also around 20,000 new cases of AML.
Magrolimab is out in front among a small but growing group of companies developing CD47-targeting immunotherapies for cancer. Others include Trillium Therapeutics, I-Mab, Innovent, ALX Oncology, Surface Oncology, Vivoryon and Morphiex.
Trillium also reported new phase 1 data with its candidate TTI-622 in patients with advanced relapsed or refractory lymphoma at ASCO, backing up the tolerability of the drug and showing glimpses of efficacy including two partial responses in heavily pre-treated diffuse large B-cell lymphoma (DLBCL) patients.

Gilead trumpets data with newly-bought magrolimab in blood cancers

Asco 2020 – Enhertu impresses, but can it live up to high hopes?

As three Asco presentations confirm the Her2-targeting agent’s potency, Daiichi Sankyo and Astrazeneca lay out an ambitious development programme.

Enhertu is associated with some very big numbers: the $1.4bn that Astrazeneca paid Daiichi Sankyo to secure rights to the Her2-targeting agent, and the billions in sales that the sellside forecasts, for example. In the clinical realm at Asco this year, response rates reported in three tumours were also impressively high.
While analysts’ sales projections were arguably swelled by the deal terms, very competitive efficacy is harder to refute. Two physicians discussing Enhertu data at virtual Asco over the weekend acknowledged as much. However, with lung toxicities still leading to patient deaths, despite this side effect being well documented, Daiichi and Astra face a challenge moving Enhertu into more valuable earlier treatment settings.
This will surely be required for Enhertu to meet current forecasts, which see global sales topping $4bn by 2026, according EvaluatePharma’s sellside consensus. It is notable that this projection comprises some very different outlooks, with the minimum and maximum forecasts around 50% higher or lower than that $4bn average.
Banks with numbers at the low end of the range assume that Enhertu will never move beyond a last-resort therapy, in certain diseases at least, where the benefits more obviously outweigh the risks. All three studies detailed at Asco concerned these types of patients, most of whom had been heavily pretreated and were running out of options.
In Destiny-CRC01, for example, colorectal cancer patients had received at least four lines of prior therapy, and some had received 11. In Destiny-Lung01 most subjects had had two prior treatments, with some on their sixth.
The lung results received perhaps the most effusive reception, and a look at the waterfall plot of responses shows why. Almost all patients responded, with objective remission rate hitting 62% and median progression-free survival hitting 14.2 months.
Dr Benjamin Levy of Johns Hopkins, reviewing the trial for Asco, described Enhertu as “the best drug in my mind that I have evaluated for Her2-mutated lung cancer”.

Dr Smit and Asco

In colorectal cancer Enhertu achieved a 45.3% response rate in patients with confirmed high Her2 positivity, and reviewing physician Dr Autumn McRee, of the Lineberger Comprehensive Cancer Center at North Carolina University, described the trial as “certainly clinically relevant”.
Still, she pointed out that it was not known whether a Her2-specific approach was superior to standard of care options in these patients – the academic-sponsored S1613 study could help answer this question – while it is also unclear whether Enhertu is a better rescue than traditional Herceptin.
Destiny-Gastric01 was also presented at Asco – this registrational study was known to have succeeded – and a four-month survival benefit over chemotherapy seems to give Enhertu a good chance of accelerated approval in this setting. Indeed, Astra and Daiichi are expected to file for quick approvals in all of these three tumour types.

Enhertu’s lung toxicity profile: a cap on use?
	Destiny-CRC01 (n=78)	Destiny-Lung01 (n=42)	Destiny-Gastric01 (n=125)	Late-stage breast cancer (rates on US label, n= 234)
ILD occurances (%)	5 (6.4%)	5 (11.9%)	12 (9.6%)	9%
Deaths from ILD	2 (2.6%)	0	1* (0.8%)	2.6%
*Pneumonia. Source: Asco presentations & US drug label.

The specific toxicity associated with Enhertu is interstitial lung disease, and related pneumonia, and this side effect was seen across all studies presented at Asco. Rates were in the same ballpark as those seen in the breast cancer studies that won Enhertu approval, with the drug being attributed to three deaths. It is clear why much more consideration will go into backing this drug in less sick patients.
Breast cancer will be the first indication to yield results in earlier settings, with three studies recruiting second and third-line patients. Destiny-Breast02, Destiny-Breast03 and Destiny-Breast04 are all still recruiting, with first data expected in 2021, Astra confirmed to Vantage.
The ’04 study is particularly interesting as it selects patients with low Her2 expression. Earlier studies confirmed Enhertu’s effectiveness in these patients, who do not typically respond to existing Her2-targeted agents, and the drug’s developers have made much of its purported ability to extend the reach of Her2 targeting. Still, it is notable that at Asco it was revealed that two exploratory cohorts of low Her2 expressers in Destiny-CRC01 had failed to respond to treatment.
Destiny-Gastric01 also stratified patients by Her2 expression, although these subgroups have yet to be detailed. Astrazeneca declined to share the results with Vantage, saying data would be presented at later medical meetings, and a spokesperson said the lack of signal in CRC01 should not be read through to other trials.
On a post-Asco call Daiichi laid out an ambitious clinical programme for Enhertu, including 17 new clinical studies, encompassing first-line trials in breast, lung and gastric cancers. It seems that a low Her2 strategy is only being pursued in breast cancer, however.
Targeting low Her2 expressers is not Enhertu’s only USP, of course; the drug has elicited responses in patients who had failed on mechanistically similar agents. But with a side-effect profile already threatening to cap its potential, neither Astra and Daiichi, nor analysts defending sky-high sales forecasts, will want to see a trial like Destiny-Breast04 fail.
https://www.evaluate.com/vantage/articles/events/conferences/asco-2020-enhertu-impresses-can-it-live-high-hopes

I-MAB advances repositioned RA drug in early trial for Covid-19 cytokine storm

Several weeks after the COVID-19 pandemic rolled across the globe, the term “cytokine storm” started popping up in medical reports from physicians treating the disease. The emergence of the syndrome—a hyperactive immune response that can be deadly—prompted several companies to scour their product portfolios and pipelines for drugs that might be able to target it.
China-based I-MAB Biopharma, fueled by a recent $104 million initial public offering, has joined the effort to speed medicines to market that can treat cytokine release syndrome. The company said last week that it saw positive results from a small clinical study of its experimental drug TJM2 and is progressing to part two of the study.
TJM2 is an antibody that inhibits GM-CSF, a cytokine that’s known to contribute to tissue inflammation and degeneration in diseases such as rheumatoid arthritis (RA). It’s a different mechanism of action than Roche’s Actemra, which is an IL-6 inhibitor that has been snapped up during the pandemic to treat patients with cytokine release syndrome.

In part one of I-MAB’s trial, 24 patients were randomized to receive one of two doses of TJM2 or a placebo. The company didn’t provide many details about the results except to note a “correlation between clinical improvement and reduced levels of some disease related cytokines.”
The higher of the two doses of TJM2 will be tested against a placebo in the next phase of the study, which will include 120 patients, the company said. I-MAB recently completed a phase 1 safety study of the drug in healthy volunteers in the U.S.

Studies of COVID-19 patients have documented high levels of both GM-CSF and IL-6 in the bloodstream of those who become severely ill, said Jingwu Zang, founder of I-MAB, in a conference call with analysts about the clinical trial plan. “While our goal remains to develop TJM2 in rheumatoid arthritis and other autoimmune conditions, there is strong scientific evidence to suggest that inhibiting GM-CSF may have a beneficial impact on patients with cytokine release syndrome … associated with COVID-19,” he said.
I-MAB does have an IL-6 inhibitor in phase 2 trials to treat ulcerative colitis and other diseases, leading one analyst to ask during the call why the company chose to pursue TJM2 in COVID-19 instead.
“In terms of the mechanism of action, GM-CSF works upstream in the pro-inflammatory cytokine network,” Zang said. “It sits above IL-6. So targeting GM-CSF not only inhibits IL-6, but also other inflammatory cytokines that play an important role in cytokine release syndrome.”
Several companies are stepping up to address cytokine release syndrome in COVID-19. In April, the FDA granted emergency approval to a device that strips inflammatory cytokines out of the blood. Novartis and Incyte are testing their JAK inhibitor Jakafi for treating the syndrome, and Roche said last week it would launch a trial combining Actemra with Roche’s recently approved remdesivir in patients with severe COVID-19 pneumonia.
I-MAB may not be as big a name as other COVID-19 players, but it does have a large network of backers. Prior to its January IPO, it raised more than $400 million from C-Bridge Capital, CDH Investment and several other private investors who were attracted to its strategy of advancing multiple phase 2 and 3 trials simultaneously.
I-MAB’s executives said during the call that if the results of part two of the TJM2 study in COVID-19 are positive, it will consult with the FDA to develop a plan to speed the drug to market. The company is also accelerating a manufacturing plan to ensure it will have enough of the drug for further clinical trials and to meet the public demand, they said.
https://www.fiercebiotech.com/research/i-mab-advances-repositioned-ra-drug-early-trial-to-treat-covid-19-cytokine-storm

Trump trade adviser calls for more drug manufacturing in Puerto Rico

The COVID-19 pandemic has underscored key weaknesses in the biopharma industry’s complex global supply chain, and now a top adviser for the Trump administration is calling on Congress to push for more manufacturing in Puerto Rico.
In an interview with the Washington Examiner, White House trade adviser Peter Navarro faulted a “broken system” that pushes manufacturing offshore. He called on Congress to use the next round of COVID-19 relief to incentivize manufacturing on the island territory.

Previously, a tax provision allowed U.S. companies to avoid paying federal taxes on profits from operations in Puerto Rico, but Congress phased that out over time, the Examiner reports. Plus, utility costs are significantly higher there than in the U.S., which has also led to a reduction in manufacturing. Pharma companies themselves have shuttered a number of drug plants in Puerto Rico in recent years.
“If this crisis has taught us anything across party lines, it is that we do indeed need to bring home the pharmaceutical supply chain, that it is not just a public health issue, but a national security issue and an economic security issue,” Navarro told the publication.

The Trump administration has already made moves to bolster U.S. drug production in its response to the pandemic. The administration picked a little-known startup, Phlow Corporation, for a $354 million contract to produce generic meds and active pharmaceutical ingredients for COVID-19 therapies. And Monday, the government inked a $628 million deal with Maryland biotech Emergent BioSolutions for potential COVID-19 vaccine manufacturing.
Aside from the administration’s efforts, lawmakers are working on their own measures to bring drug production back to the U.S., Stat reports. That’s caused pharma companies to mobilize lobbyists to push back.
https://www.fiercepharma.com/pharma/fiercepharmapolitics-trump-trade-advisor-citing-broken-system-calls-for-more-drug

Thailand races to create COVID vaccine, eyes possible medical tourism boost

Momentum is building behind Thailand’s push to create its own coronavirus vaccine, with more manpower and resources dedicated to the effort amid hopes it could boost medical tourism.
Thai trials of an experimental vaccine using monkeys started last month, one of at least 100 potential vaccines being developed globally. The government is hopeful it will have a cost-effective vaccine ready for next year.
Bionet-Asia, a local firm working with the government and a top Bangkok university, has put all other activities on hold and dedicated 250 personnel and all of its labs, technology and production facilities to developing a COVID-19 vaccine.

“In the case of COVID, there is a global effort to speed up experiment, trials, to share information, share diagnostics and that’s why we are in a position too, to move very fast,” chief executive officer, Pham Hong Thai, told Reuters.
He said tests on animals had so far shown encouraging results and the next step would be seeking government approval for clinical trials involving humans.
With just over 3,082 cases and 57 deaths, Thailand has had some success in containing the coronavirus and eased many of its restrictions in response to low infection numbers.

It has been seven days without a case of local transmission, with all infections this past week found among quarantined nationals returning from overseas.
Public Health Minister Anutin Charnvirakul said it was important to channel all efforts towards the development of a vaccine and put Thailand on the medical map.
“Thailand has a good healthcare system, good medical practices. It will garner a lot of interest from tourists and investors and boost us as a medical hub,” he said.
https://www.reuters.com/article/us-health-coronavirus-thailand-vaccine/thailand-races-to-create-covid-vaccine-eyes-possible-medical-tourism-boost-idUSKBN2382BW