Lundbeck sells off flopped Alzheimer's drug as Aduhelm approval ups interest

 Taking a cue from the many Big Pharmas rushing to revive failed or mediocre Alzheimer's disease drugs, China’s Denovo Biopharma has picked up a discarded candidate from Lundbeck. 

Lundbeck has offloaded the rights to a 5-HT6 receptor antagonist that failed three phase 3 clinical trials in 2016 and 2017. Denovo has claimed the global rights, but Lundbeck will retain an option to reacquire the asset down the line.

Denovo focuses its business on resurrecting failed therapies that other companies have cast aside by taking a fresh look at different biomarker signals that may suggest efficacy in certain populations. Eli Lilly’s enzastaurin and pomaglumetad are among the prospects Denovo is trying to rehabilitate.

In the Lundbeck deal, Denovo will rescue idalopirdine, which was a key late-phase asset going into the first of three phase 3 readouts in 2016. However, neither dose improved cognitive function in patients in that initial study. When Lundbeck revealed two other phase 3 trials failed early the next year, idalopirdine looked to have joined the long, ever-growing list of discarded Alzheimer’s candidates. 

The addition of idalopirdine to the pipeline reflects Denovo's belief that the identification of a genetic biomarker for drug efficacy can enable Denovo to limit enrollment to subsets of patients in which the molecule is most likely to work. An independent analysis found idalopirdine might be more effective at high doses and in moderate Alzheimer’s subgroups, while cautioning the effect size is small.

But Denovo will now get the chance to test the idea in an environment that has become increasingly open to new—and unproven—approaches to Alzheimer's. Last month, Biogen made waves when the company's Alzheimer's disease therapy was approved by the FDA on biomarker evidence. Other Big Pharmas have scrambled back into the race with drugs they once considered hopeless. 

Denovo, which operates out of sites in Beijing and San Diego, has put together an undisclosed financial package to secure the right to test its idea. The deal gives Lundbeck the option to reacquire the asset for predetermined but undisclosed financial terms. If that happens, Lundbeck will share the rights to idalopirdine in China and control the asset outright in the rest of the world. 

Full details of Denovo’s plans for the development of idalopirdine are yet to emerge. The first step is to use a biomarker platform to look for pharmacogenomic predictors of the efficacy of the drug, now known as DB109.

https://www.fiercebiotech.com/biotech/lundbeck-sells-rights-to-alzheimer-s-drug-failed-3-late-phase-trials

Biotech Losers In 2021 That Could Bounce Big In The Second Half

 Biotech stocks are tricky investment bets that require careful analysis and scrutiny. A stock that has fallen off a cliff in reaction to a binary event can neither be written off entirely nor picked as a bargain buy. A lot of background research should go into the stock, company pipeline, cash runway, and other factors before an investment decision can be made.

Here's a list of biotech stocks that were among the worst performers in the first half but have the potential to come back stronger:

Immunovant, Inc IMVT 3.08%

Year-to-date loss: (-77%)

Immunovant is a one-trick pony. Its investigational product candidate IMVT-1401 is a novel, fully human monoclonal antibody. It has the potential to address a variety of IgG-mediated autoimmune diseases as a subcutaneous injection.

The company's shares nearly halved in early February when it announced a voluntary pause of dosing in its ongoing clinical trials. The pause followed identification of physiological signal consisting of elevated total cholesterol and LDL levels in IMVT-1401-treated patients in ASCEND GO-2, a Phase 2b trial in thyroid eye disease.

The stock came under further pressure in mid-February when it released its fourth-quarter results for 2020. The first-quarter results reported in early June resulted in more selling off. 

Upcoming Catalyst: Resumption of clinical development of IMVT-1401, including in a potentially pivotal trial in myasthenia gravis and a phase two study of warm autoimmune hemolytic anemia, could positively impact the stock. The company has indicated a late 2021 or early 2022 timeline for the resumption.

ChemoCentryx, Inc. CCXI 0.15%

Year-to-date Loss: (-77%)

ChemoCentryx, which focuses on developing inflammatory and autoimmune diseases and cancer treatments, was once a high flier. The company's shares began a downtrend in early March following its financial results for the fourth quarter of 2020.

A steeper sell-off ensued in early May following the release of a briefing document ahead of an Adcom meeting to review its new drug application for avacopan to treat antineutrophil cytoplasmic autoantibody-associated vasculitis. ANCA-associated vasculitis is the inflammation of small blood vessels that can eventually lead to organ failure due to the reduced blood flow through the inflamed blood vessel. The split Adcom verdict announced May 6 pressured the stock further.

The company has a diverse pipeline, consisting of assets targeting orphan diseases, oncology, inflammatory and autoimmune diseases, and chronic kidney diseases.

Upcoming Catalyst: Avacopan will face another key test when the FDA decides on the drug's potential approval on July 7. Expectations are muted given the lukewarm Adcom reaction. European regulators are likely to rule on the drug in the second half.

The company is also planning a Phase 3 trial of avacopan in severe hidradenitis suppurativa patients and discuss evidence of clinical benefit of avacopan in C3 glomerulopathy with the FDA following ACCOLADE results.

Sigilon Therapeutics, Inc. SGTX 2.45%

Year-to-date Loss: (-77%)

Shares of Sigilon have been on a secular downtrend since peaking at $45 in mid-February. The company's clinical programs focus on rare blood disorders, lysosomal diseases, and endocrine and other chronic diseases. Most of the pipeline candidates are preclinical assets, except for SIG-001, which is in Phase 1 development for severe-to-moderate hemophilia A.

Upcoming Catalyst: Sigilon expects to disclose up to nine months of follow-up data for three to four patients from the Phase 1/2 hemophilia A study in the third quarter of 2021. It also expects to complete enrollment of the study in the second half of 2021.

Athira Pharma, Inc. ATHA 0.47%

Year-to-date Loss: (-69%)

Athira is a clinical-stage biopharma focused on developing therapies for neurodegenerative diseases. It pursues a novel approach called neuronal health that uses small-molecule treatments designed to work by targeting specific, naturally occurring repair mechanisms.

The company's pipeline consists of ATH-1017, which is in Phase 2 development for Alzheimer's disease and Parkinson's disease dementia. It has two preclinical assets, namely ATH-1020 and ATH-1018.

Athira shares came under pressure in January after it raised $90 million through a common stock offering. From a rangebound phase, the stock dipped sharply in early June, when the company placed its then-CEO Leen Kawas on temporary leave pending a review of actions stemming from doctoral research she conducted while at Washington State University.

Upcoming Catalyst: Athira targets an IND submission for ATH-1019 and ATH 1020 by the end of 2021. The removal of the overhang over the scandal concerning its ex-CEO could also be optimistic for the stock.

Imara Inc. IMRA 2.09%

Year-to-date Loss: (-63%)

Imara, a biopharma developing therapies for rare genetic disorders of hemoglobin, saw its shares slide early this year. The negative catalyst was data from the Phase 2a clinical trial of IMR-687 in adult patients with sickle cell disease.

Following the data release, SVB Leerink analyst Joseph Schwartz said COVID-19 impacted the quality of data due to aspects such as failed hospital visits. Additionally, the dosage evaluated was much lower than the company's dose to move ahead with the Phase 2a open-label expansion and the Phase 2b studies.

According to the analyst, the dataset represented a rearward-looking view of IMR-687's development and is likely not a good indicator of the robustness of data we expect to see in IMR-687's future readouts.

"Therefore, we see the stock's weakness on the news as a potential buying opportunity ahead of IMRA's multiple data readouts in 2021," Schwartz said in the note.

Upcoming Catalyst: Imara is scheduled to report interim analyses for Ardent sickle cell disease and Forte beta-thalassemia Phase 2b clinical trials in the second half of 2021.

https://www.benzinga.com/general/biotech/21/07/21796177/biotech-losers-in-2021-that-could-bounce-big-in-the-second-half

Foxconn's Terry Gou, TSMC reach initial agreements for BioNTech vax in Taiwan

 

Terry Gou, the billionaire founder of Taiwan's Foxconn, along with TSMC reached initial agreements to each buy 5 million doses each of BioNTech SE's COVID-19 vaccine on Friday, three sources with knowledge of the situation told Reuters.

Taiwan's government has tried for months to buy the shots directly from Germany's BioNTech and has blamed China, which claims the self-ruled island as its own territory, for nixing a deal the two sides were due to sign earlier this year. China denies the accusations.

Last month, facing public pressure about the slow pace of Taiwan's inoculation programme, the government agreed to allow Gou and Taiwan Semiconductor Manufacturing Co to negotiate on its behalf for the vaccines, which would be donated to Taiwan's government for distribution.

Gou and TSMC reached the agreements with a subsidiary of Shanghai Fosun Pharmaceutical Group Co Ltd, which has a contract with BioNTech to sell the COVID-19 vaccines in China, Hong Kong, Macau and Taiwan, the sources said.

The deal is not final and will still take some time to close the deal, one source said.

It includes "related legal documents" needed to finalise the deal but does not specify a delivery date, as global demand for vaccines continues to outstrip supply, this person said. 

The vaccines will be shipped directly to Taiwan from the German manufacturer, the person added.

Taiwan's government has said any BioNTech vaccines should be "produced in the original factory with the original packaging" and be directly delivered to Taiwan.

Fosun did not respond to a request for comment.

Foxconn, a major Apple Inc supplier, said it was continuing to "work hard" on the vaccine purchase plan. It did not elaborate.

TSMC said in a brief emailed statement it was still a work in progress and "no further information is available at this time".

BioNTech declined to comment.

Taiwan Health Minister Chen Shih-chung said on Saturday the government was very thankful for the hard work Foxconn and TSMC were putting into getting the shots but that buying vaccines was "quite difficult" and the process challenging.

Another source said the German government, which has said it was trying to help Taiwan obtain the BioNTech vaccines, had been trying to speed up the talks.

"The German government doesn't want to leave the impression that they didn't sell vaccines to Taiwan due to the Chinese pressure, so it has been pushing the company to speed up its talks with Taiwan," the source said, referring to BioNTech.

The German Foreign Ministry declined to immediately comment.

Both sources said although global supplies are tight, Fosun, as an exclusive dealer for the vaccine in China and Taiwan, is able to secure higher priority for the vaccine distribution.

Only around 9% of Taiwan's 23.5 million people have received at least one of the two-dose COVID-19 vaccine regimen, a need made more urgent by a spike in domestic infections on the island, though numbers remain relatively small.

https://www.marketscreener.com/business-leaders/Terry-Gou-1167/news/Exclusive-Taiwan-s-Terry-Gou-TSMC-reach-initial-agreements-for-BioNTech-vaccines-sources--35778103/

Asking Good Questions In Your Trading

 

In recent meetings with traders, I've heard a similar question:  When are stocks going to come down?  Those traders have been frustrated by the seeming steady march higher, as time and again, they have tried to sell "overbought" stocks and indexes.

When I hear the same question again and again, I've found it's usually the wrong question.

Here's an example of a good question, which I define as a question coming from a fresh, unexpected perspective:

"Last week, we saw a majority of SPX stocks trading below their 50-day moving averages, according to the Index Indicators site.  After such a correction, what has the market done when we've returned to a situation where over 50% of stocks are trading above their 50-day moving averages?"

Note why this is a good question:  It ignores what the chart looks like and instead defines correction as any period in which the majority of stocks trade below their moving average.  By that definition, a correction has already occurred, even though it looks as though we've simply moved higher.

Good questions often are grounded in what is not obvious.

Well, according to the backtesting function of Index Indicators (see the MarketCharts.com site for even more extensive backtesting), we've had 10 instances over the past two years in which stocks have traded below their 50-day moving averages and then crossed back above.  All 10 instances were profitable 10 days later, by an average of +3.16%.  Indeed, just these 10 instances accounted for well over half of all SPX gains over the two year period.

So far, it's been a good trade.

To be sure, 10 instances does not constitute proof, and one would not build an algorithmic trading system on such limited data.  But I'm not looking for proof or systems; I'm looking for promising hypotheses.  Once I have those and I notice that everything I look at intraday is confirming the hypothesis, I have an idea worth trading.  

Very often, when I have traded poorly, I have not grounded my trading in good questions.

There's no sense working on your "trading psychology" if you're looking at the same charts and trading the same way as everyone else.  Our edge comes from uniqueness of perception and analysis.  That's true in every human endeavor.

https://traderfeed.blogspot.com/2021/07/asking-good-questions-in-your-trading.html

How Has The Flood Of Information Changed Wall Street Since 1990

 In a world where Wall Street admits that it increasingly gets its most precious commodity - information - from social networks such as Twitter, Reddit and Facebook...

... it got us thinking about the changing nature of information flow in finance and how it may be impacting markets.

Conveniently, in a recent note from DataTrek's Nick Colas, the former SAC portfolio manager takes a big picture look at just this topic, writing that when he started covering stocks in 1991 back at Credit Suisse, there was no Internet, no smartphones, no “Big Data”, no quarterly earnings conference calls, and no real regulation around how companies disseminated potentially market-moving information. All those things exist today, and according to Colas, the fact that the world's financial decision-makers are flooded with instant (and constant) information may well explain part of why US stocks trade at such premiums to prior cycles. But, as Colas also notes, more information can also make investors overconfident.

Below we excerpt from the DataTrek founder's latest note about the changing nature of information as it relates to the investment process over the last 30 years.

Too Much Information, by Nicholas Colas

We’ll start in late 1991 when these words first came out of a CFO’s mouth: “We should do a conference call after the quarter.” The speaker was Jerry York, then Chrysler’s chief financial officer. The company had just done a “save the firm” equity issuance to fund production of the then-new Grand Cherokee.

He felt that the institutional buyers of that deal should hear directly from the management team right after Q4 earnings were made public. They had taken a big risk buying Chrysler, which at the time was essentially insolvent. Keeping the lines of communication open with this group of investors was important. After all, the company might need to tap them again if the US economy didn’t continue to rebound.

I was at that first call, which was a hybrid in-person/teleconference held at the old Sky Club on top of what was then the Pan Am building in New York City. Some big investors in the deal traveled to New York to attend, and others dialed in. It did what Jerry wanted. Investors got to ask their questions directly and also hear management’s take on the business.

As effective as that form of shareholder communications was, quarterly earnings conference calls only slowly caught on through the 1990s. For many years, analysts more commonly waited for earnings reports to come through on PR Newswire. We would then print those out on a dot matrix printer and call the company’s CFO or investor relations person. We’d then wait for a call back and ask our questions about the numbers. Sometimes it would be the same day, sometimes the next. And if the company didn’t like you, that return call would simply never come.

Other differences between 1991 and now, as far as the investment process goes:

• No Internet back then, at least as far as its utility to Wall Street. No Google, no Wikipedia, no “Big Data”.
• No smartphones. If you were on the road and wanted a price quote or the latest news, you called your trading desk.
• No email – analysts’ reports were printed and mailed/messengered to clients.
• No Fed press conferences after FOMC meetings. Only Fed Chair Alan Greenspan spoke on policy, and infrequently at that.
• No regulations requiring analysts to share their views with all clients at once.
• No regulations requiring that companies disseminate market-moving information broadly. Most just used their favorite Wall Street analysts to update investors on earnings guidance.

I think about all these differences every time I look at a 1990 – present history of the CBOE VIX Index. Has more, and more-widely available, information made US stocks less volatile? In theory, it should. Volatility is, first and foremost, a function of how much relevant fundamental information is embedded in stock prices.

Here’s that VIX history back to 1990, which shows that the period from 2012 to 2019 did see generally lower volatility than the prior 2 economic up cycles. There were other forces at work, certainly … A long expansion makes for more predictable corporate earnings, which should make for lower equity price volatility. But seeing a VIX that reliably traded below 19 (its long run average) for the better part of a decade is still notable. The truly “different” thing about this period versus the previous ones is the change in the quantity and speed of information flow.

What’s also striking about that chart is that volatility shocks (which always bring lower asset prices) still routinely occur despite the much greater amount of information available to markets and investors. Chalk that up to human nature. Prospect Theory says humans “feel/fear” loss about twice as much as equivalent gains. That asymmetry explains the old trader’s saying that “the market takes the stairs up, but the elevator down” when an unexpected event occurs.

Now, what does all this mean for current US equity market dynamics? Three thoughts:

1. Everything else equal, more complete information about company/macro fundamentals should make for higher equity valuations now relative to prior cycles. It’s hard to prove statistically that this is the case, but it makes intuitive sense to me.
2. More information now should also allow markets to reset more quickly after a shock than prior cycles. Imagine if we’d had the Pandemic Recession in pre-Internet 1990 instead of 2020. Would investors have as much confidence in a global economic recovery if they couldn’t see it forming through data from Google Trends, smartphone-enabled mobility tracking, and other 21st century sources of data? I doubt it.
3. Greater levels of available information can, however, lead to investor overconfidence.

We’ll close out with a cautionary tale about “too much information” that relates to that last point:

• Back in the 1970s, US researchers ran a study with 8 professional horse racing handicappers as their subjects.
• They had the subjects list all the horse-specific datapoints they found most useful in predicting the outcome of a race, ranked from most to least important.
• The handicappers received their top 10 data choices for the horses in an upcoming race and were asked to predict the winners.
• For the next race, they saw their top 20 choices and made predictions based on that now-larger base of information.
• Finally, they got their top 40 choices for relevant predictive data and forecast the outcome of the last race.

The surprising finding: while the handicappers’ confidence about their predictions increased with larger amounts of information, their accuracy in picking winners did not.

The lesson, profoundly relevant to investing: use the wealth of information available in a 21st century world with caution. More is not always better.

https://www.zerohedge.com/markets/how-has-flood-information-changed-wall-street-1990

Don't expand Medicare to cover dental benefits

 Congressional Democrats are currently considering expanding Medicare to cover dental services, but their plan fills the wrong gap. Though major unmet needs exist in dental care for the poor, the proposed expansion would cost an estimated $60 billion per year when fully phased in—four times more than what Medicaid currently spends on dental services—while doing little to make care more attainable to those who most need it. The proposal would also undermine the growth of Medicare Advantage, which has significantly increased the proportion of Medicare beneficiaries with dental coverage without imposing any such cost increase on taxpayers.

Despite its flaws, the proposal is rising to prominence. Senator Bernie Sanders has been pushing for Medicare to cover dental procedures for many years, and now can advance the plan as chairman of the Senate Budget Committee. Senate Majority Leader Charles Schumer (D-NY) is flirting with Sanders’s proposal as part of a potential $6 trillion spending package. If the legislation that passed the House in December 2019 as Section 601 of the H.R. 3 drug-price-control bill is any guide, the proposal would expand Medicare Part B to cover 80 percent of the cost of twice-yearly preventive dental care (oral exams, x-rays, cleanings) and basic procedures (fillings, extractions) and 50 percent of the cost of major dental services (root canals, crowns, dentures).

Gaps in dental coverage do exist. Though poor oral health can exacerbate or lead to other medical conditions, dental coverage was specifically excluded by statute from the traditional Medicare benefit, except where associated with major inpatient procedures. Whereas Medicare is responsible for 26 percent of hospital expenses, in 2019 it covered only 1 percent of dental costs.

Dental insurance is a recent phenomenon whose prevalence post-dates the creation of Medicare. As recently as 1962, only 0.5 percent of Americans had such plans. It was long thought to be a routine, low-variance expense for which individuals had less reason to pool risks to protect themselves from catastrophic costs. As employer-sponsored dental coverage is eligible for the same tax exemption as other health insurance, 66 percent of working-age adults, but only 34 percent of seniors, had such coverage in 2015.

But Medicare Advantage has since led to rapid gains in coverage for seniors. Such plans can attract enrollees by using whatever savings they generate in efficient procurement of medical services to offer supplemental benefits, including dental. The proportion of Medicare beneficiaries enrolled in Medicare Advantage has soared from 13 percent in 2005 to 43 percent in 2021; of these, 89 percent are enrolled in plans that cover preventive dental services, while 65 percent receive comprehensive dental coverage. In 2016, the Kaiser Family Foundation estimated that 18 percent of seniors received dental coverage through Medicare Advantage—already more than all other sources of coverage put together. This year, 38 percent of Medicare beneficiaries will receive dental coverage from Medicare Advantage. As a result, it’s likely that most seniors now have dental coverage, with Medicare Advantage benefits being spread more evenly across the income spectrum and offering the most generous coverage to low-income seniors.

Today, the distribution of unmet needs for dental care has more to do with income than with age. Sixty-five percent of seniors received dental care in the past 12 months, similar to the figure for working-age adults. Even before the rapid growth of Medicare Advantage, seniors were less likely to have untreated cavities than were working-age adults. Thirty-three percent of working-age adults with incomes under the Medicaid eligibility cutoff, compared with only 6 percent of seniors with incomes above that cutoff, cited financial barriers as a reason for failing to obtain needed dental care.

It is Medicaid that falls short of delivering adequate dental care to those it is supposed to be helping. Spending on dental services under Medicaid is highly concentrated on low-income kids, whom states are required to cover, and is typically slim or nonexistent for seniors, whom they are not. While 39 percent of children in 2015 received dental coverage under Medicaid, only 7 percent of adults did. Just 36 states currently cover preventative or restorative dental procedures under Medicaid for low-income adults, including seniors. In 2014, Medicaid payments for dental services averaged 40 percent of rates paid by private insurers. As a result, only 43 percent of dentists currently accept Medicaid patients, even when beneficiaries are nominally eligible.

Recent changes haven’t helped. As the Affordable Care Act’s expansion of Medicaid eligibility to childless adults was unaccompanied by increases in dental reimbursement rates, the increase in dental visits that it caused among childless adults seems to come at the cost of a decline in access to dental care among previously eligible adults. Medicaid’s dental benefits and reimbursement rates typically suffer retrenchment during periods when state budgets are squeezed.

The Democrats’ proposed dental benefit would cost more than four times the $14 billion that Medicaid currently spends on dental care every year—aid that would not be targeted to those who most need it. Though the proposal would assume the bulk of dental costs for wealthier seniors, substantial coinsurance would likely continue to deter poorer enrollees from seeking treatment. States may still be unforthcoming with the funds needed to help them.

A better solution is possible. Expressing opposition to a universal dental benefit under Medicare, the American Dental Association once stated: “Congress should target whatever limited federal resources are available toward robust and adequately funded Medicaid coverage for poor adults, which would include many seniors.” That’s the right approach—and the rapid growth of dental coverage for Medicare beneficiaries through Medicare Advantage, funded with efficiency gains rather than extra costs, only adds to its wisdom.

Chris Pope is a senior fellow at the Manhattan Institute.

https://www.city-journal.org/dont-expand-medicare-to-cover-dental-benefits

Sellas: Promising Data from Combination Trials in Ovarian Cancer, Mesothelioma

 Positive results from Sellas Life Sciences Group’s Phase I/II trial using galinpepimut-S (GPS) as a combination therapy with pembrolizumab (Keytruda®) were announced Wednesday, shortly after similarly positive news was issued from a combination study in which GPS was evaluated as a treatment for mesothelioma.

Although both trials are small – 11 and 4 persons, respectively – they are part of a broad strategy that involves multiple studies to investigate GPS as a therapy for several conditions. In that context, their results support each other and Sella’s overall effort to gather safety and efficacy data from diverse patient populations.

GPS is a Wilms Tumor-1 (WT1)-targeting peptide immunotherapeutic. For the ovarian cancer study, it was used in combination with the checkpoint inhibitor Keytruda® to treat patients diagnosed with second- or third-line WT1(+) relapsed or refractory platinum-resistant, advanced metastatic ovarian cancer. Of the 11 patients in this study, nearly 67% had failed second-line therapies or were refractory, and all were resistant to the standard of care platinum-based therapy. They were expected to survive 9 to 12 months.

An ad hoc analysis at 15-week follow-up showed that nearly 64% of the patients were stable or are responding to the combination therapy. More than nine months after their initial treatment, all 11 are still alive. Median overall survival, therefore, remains unknown.

Preliminary evidence from the Phase I trial of GPS administered as a combination therapy with nivolumab (Opdivo®) as a treatment for mesothelioma showed improvement in median survival of about half a year. Sellas reported median survival of 35.4 weeks after one month of GPS treatment, compared to 28 weeks for patients receiving standard of care (pemetrexed, a chemotherapy), for relapsed/refractory patients. This trial involved only four patients, however.

Such gains are “signals that a combination approach could have a benefit for patients,” Angelos Stergiou, M.D., Sc.D. h.c., president and CEO of Sellas, told BioSpace.

“The fundamental news from the mesothelioma study is that it seems to be safe and tolerable,” Stergiou said. “We went after a very serious disease state and showed a meaningful survival rate, even in the one patient with the sarcoma-toid variant.” That patient was diagnosed with Stage IV cancer and, so far, has survived 25 months – several months longer than usual for those receiving standard of care. (The expected survival for this patient under standard of care treatment was 12 to 18 weeks.)

“We expect to have follow-up data by the end of the year in a large patient sample,” he added.

“Sellas specializes in immunotherapy focused around the development of Wilms Tumor 1 antigen, which was designated as the number one immunotherapy target by the National Cancer Institute,” he said.  WT1 antigen is expressed in the cell nuclei of 75% of mesotheliomas and 93% of ovarian serous carcinomas, for example. There are approximately 20 tumor types that overexpress WT-1 antigen, thus suggesting GPS could have substantial application.

GPS is made of four peptide chains. Two of those (CD4+ and CD8+) induce a strong innate response against the WT1 antigen and access multiple HLA types. When administered, therefore, the immune system recognizes and destroys cancer cells and can continue to do so, targeting recurring tumors and residual cancer cells. Consequently, Stergiou said, “Patients can stay in remission longer and, hopefully, this will translate into longer overall survival.”

In most cases, GPS is not envisioned as a stand-alone therapy. “GPS, when used alone, isn’t built to debulk tumors,” he said. Instead, it works synergistically with immunotherapies – notably, Opdivo® and Keytruda® – that modulate the hostile tumor microenvironment. Then, when GPS is injected, “GPS increases the antigen-specific effector T cells and shepherds them, focusing the immune response to specific epitopes for optimal T cell response,” Stergiou said.

Based on that mechanism of action, GPS may have potential as a monotherapy for patients who are in complete remission. That hypothesis is being tested in the ongoing Phase III study of AML patients.

“Our lead program (currently in Phase III) is in acute myeloid leukemia for patients in their second remission,” Stergiou said. Earlier, Phase II data, showed notably longer survival rates for patients in their second complete remission – 21 months for those receiving GPS therapy versus 5.4 months for those receiving standard of care treatment.

The Phase III program began in January. It is a 1:1 randomized, open-label study comparing GPS monotherapy in the maintenance period to investigators’ choices of therapy in ALS patients who have achieved complete remission after second-line antileukemic therapy, and who are ineligible or unable to participate in stem-cell transplantation. Ultimately, Sellas plans to enroll 116 patients across 50 clinical sites in the U.S. and Europe.

https://www.biospace.com/article/sellas-reports-promising-data-from-combination-trials-in-ovarian-cancer-and-mesothelioma/