Search This Blog

Sunday, April 10, 2022

There Is No Correction In Low Volatility Large Caps

 Despite increased selling pressures in the S&P 500, NASDAQ-100, and Russell 2000, low volatility large caps reached new highs this week.

The chart below depicts the S&P 500 total return index since 1972.

The index made new, all-time highs this week as it closed above its December 2021 highs. The table below makes a comparison with the three popular stock indexes.

Total Return IndexesDrawdown*Year-to-Date
S&P 500 Low Volatility0%+1%
S&P 500-6.1%-5.5%
NASDAQ-100-13.3%-12%
Russell 2000-17.9%-10.9%

* As of April 8, 2022. This is not maximum drawdown for the year, or historically. 

In the past, there has been divergences between the S&P 500 low volatility large caps and the S&P 500 large caps, but not always in predictable ways. For example, before the dot-com bear markets, low volatility made a top in June 1999 and about 10 months before the S&P 500 made its top. Low volatility had returned to new highs by September 2020, but the S&P 500 had entered a bear market. Then, low volatility continued to make new highs until March 2002, when it finally reversed. Maximum drawdown for S&P 500 was about 48% but for low volatility it was about 23%, both on a total return basis.

I think the explanation is simple: large funds will never go to a 0% allocation for stocks if a bear market develops, but instead reduce exposure and shift to lower risk stocks because the timing of the rebound is unknown.

In addition, these divergences offer present long/short opportunities, but also, in this case, timing is of the essence.

https://www.priceactionlab.com/Blog/2022/04/low-volatility-large-caps/

A blueprint for boosting K-12 science education in the US

 A massive infusion of taxpayer funding for local school districts to overcome pandemic learning losses represents a major opportunity to bolster ailing K-12 science education in the U.S.

Covid relief bills are providing some $192 billion for schools, roughly six times the amount of the 2021 base federal funding to schools. Local communities and educators should seize on this unique moment to set a new trajectory for all students across the country, wherever they live and whatever their backgrounds.

Science-focused education is among the greatest levers to accessing opportunity and is unmatched in unlocking student potential. But in many locales around the country, science is taught as an afterthought, what Dr. Margaret Honey, president and CEO of the New York Hall of Science, calls an “anemic” teaching approach .

“We teach it as a memorization exercise. We don’t teach it as a domain of inquiry and problem-solving and question-asking — all of the skills that are essential in today’s world,” she said during a recent panel discussion on K-12 science education by the Collaborative for Student Success. “That’s criminal.”

At the National Math and Science Initiative, a non-profit that works with local, state and national partners to increase educational opportunities for all students, our strategy for improving the quality of STEM education is yielding dividends around the country.

We believe it can serve as a model for others to adopt:

First must be a major focus on getting all kids the knowledge and skills to succeed in Advanced Placement science and math classes, where they evolve into students ready to take on the challenges of college. Our own College Readiness Program, with its emphasis on AP science and math, has reached more than1,400 public high schools across 36 states and D.C. and resulted in very positive student outcomes across the range of school settings — urban and rural, traditional and charter.

After one year of the program, partner schools see an average 41 percent increase in AP participation and an average 35 percent increase in college readiness for all students, with similar increases for female, Black and Latino students. When students are ready for college, they are more likely to graduate from college. And when they are better grounded in science and math and have the confidence that AP classes affords them, they are more likely to consider degrees in those fields.

Second, school districts must lay the foundation for student success by ensuring that K-12 educators have the skills and high-quality instructional materials required to teach STEM more effectively. In our own effort led by expert educators, teachers build and maintain subject matter expertise in science and math, enhance their leadership skills and prepare students to be creative problem solvers. We have trained more than 65,000 teachers in STEM thus far. Confident teachers create confident students eager to explore science and math in college.

Third, the nation needs more STEM teachers, especially teachers of color. The data show that educational outcomes improve significantly for Black students when they have as few as one black teacher. Yet only 6 percent of secondary STEM teachers identify as Black.

A proven model for boosting the pipeline is the work done by the University of Texas and its UTEACH Institute. The program promotes collaboration among college-level education, math and science departments to introduce STEM majors to teaching and prepares them to become highly qualified teachers.

My organization and the UTeach Institute are working with leaders at 45 universities to create UTeach programs across the country. We are also working alongside 10 Historically Black Colleges and Universities to create programs for teacher preparation on those campuses. The effort aims to significantly increase the number of highly qualified Black STEM teachers in American schools.

Science is the wellspring from which our modern life and economy blossom. From covid vaccines to blockchain, mobile phones to space exploration — all these innovations began as an idea coaxed into existence by people rooted in science. And people who have succeeded in science often tell a story of that one inspiring science teacher in elementary, middle or high school who opened the door to the future. It is no overstatement to say that for the sake of the nation, we need millions more of those stories.

A former NASA astronaut, Harris is a physician and CEO of the National Math + Science Initiative, which is based in Dallas.

https://thehill.com/blogs/congress-blog/3263058-a-blueprint-for-boosting-k-12-science-education-in-the-us/

Almost 2 in 3 rate US economy as bad: CBS poll

 A majority of American voters rated the economy as bad, adding that higher prices have been difficult as inflation hit a 40-year high last month and gas prices continue to skyrocket.

In a new CBS News poll, 63 percent of voters rated the national economy as bad, with 66 percent saying that the higher prices have been difficult or a hardship in their personal lives. Twenty-six percent said the high prices were inconvenient and eight percent said it had no effect.

Among those who rated the economy bad, 86 percent said it was because of inflation, closely followed by gas prices at 82 percent. Sixty-nine percent said the economy was bad due to shortages of products and services, and half said it was because they do not trust the Biden administration.

The higher prices have also led Americans to save where they can, with 66 percent saying that they had to cut back on entertainment, travel and activities. The higher prices have also led 64 percent to drive less and 53 percent to cut back on food or groceries.

On lowering gas prices, 65 percent of voters say that President Biden can do more, while 35 percent say he is doing all he can.

Despite the low rating on the national economy, 56 percent of voters said the local job market was good, with 51 percent saying that U.S. jobs have increased over the past year.

The high rating comes as the demand for workers and the strong consumer spending helped power job growth. In February, the U.S. added 678,000 jobs and the unemployment rate dropped to 3.8 percent.

https://thehill.com/blogs/blog-briefing-room/3263454-almost-2-in-3-rate-us-economy-as-bad-poll/

Growing Number Of States Changing How They Report COVID-19 Hospitalizations

 by Jack Phillips via The Epoch Times (emphasis ours),

An increasing number of states and municipalities are changing how they report COVID-19 hospitalizations, cases, and other data, signaling a shift in how policymakers healthcare workers view the virus.

For example, in New Hampshire, the state reported seven COVID-19 hospitalizations, down from about two dozen reported during the previous week. Officials said the drop reflects a change in the statewide reporting policy.

In an announcement Tuesday, the state Department of Health and Human Services said it now defines a COVID-19 hospitalization to include patients who are being treated with either dexamethasone or remdesivir, which is employed to treat patients with severe or moderate symptoms. Individuals hospitalized with milder symptoms or for another reason but incidentally tested positive for the virus are not being counted, officials said.

In another sign that the pandemic is shifting, the Indiana Department of Health on Wednesday released new COVID-19 dashboards that will be updated fewer times per week. As for COVID-19 hospitalizations, the state will now only display the number of individuals who are hospitalized and won’t show the percentage of intensive care unit beds or ventilators available in the state.

“The increased use of at-home tests and other antigen tests that are never reported to the state has diluted the value of posting a daily positivity rate,” Chief Medical Officer Dr. Lindsay Weaver told local news outlets. “A better measurement is the impact that COVID-19 is having on our health care systems, and our dashboard revisions will make it much easier to see how hospitals are being impacted.”

Meanwhile, Ohio Department of Health (ODH) Director Bruce Vanderhoff said on March 10 that Ohio is transitioning from daily to weekly COVID-19 data reporting, including cases, hospitalizations, and deaths.

As cases and hospitalizations dramatically decline, we are refining our public reporting processes to be more relevant for this new phase of the pandemic,” he said.

Around the same time, health officials in Nevada said they would reduce how often the state reports COVID-19 cases, deaths, and hospitalizations.

“Just as the COVID-19 pandemic has evolved over time, the public health response has also evolved in response to both changes within the virus and the way we measure community and health care impacts,” Nevada state epidemiologist Melissa Peek-Bullock said on March 10.

Arizona on April 7, meanwhile, said it would be scaling back updates of COVID-19 hospitalization data displayed on the state’s CCP (Chinese Communist Party) virus dashboard in the wake of the diminishing of the outbreak and Gov. Doug Ducey’s recent end of the state of emergency that he declared over two years ago

Department of Health Services Director Don Herrington said Thursday in a blog post that a surveillance order requiring hospitals to report specific COVID-19 data is no longer in effect. Ducey lifted the order on March 03.

The end to updates of graphs displaying data on hospital bed usage availability, specific metrics for COVID-19, and ventilator usage and availability comes as COVID-19 hospitalizations have lessened significantly since the omicron variant’s peak in January, Herrington said.

“There are normal changes in operations as public health transitions to its traditional role of disease surveillance, prevention, and control,” Herrington said. “These changes to the dashboard reflect that.”

The Associated Press contributed to this report.

Ukraine conflict hurts Russian science, as West pulls funding

 Dozens of international scientists have arrived each year since 2000 at Russia's remote Northeast Science Station on the Kolyma River in Siberia to study climate change in the Arctic environment.

Not this year, though.

Following Russia's invasion of Ukraine, Germany's Max Planck Institute for Biogeochemistry froze the funding used to pay personnel at the research station and to maintain instruments that measure how quickly climate change is thawing Arctic permafrost and how much methane - a potent planet-warming gas - is being released.

The funding freeze will probably lead to an interruption of the continuous measurements at the station dating back to 2013, compromising scientists' understanding of the warming trend, said Peter Hergersberg, a spokesperson for the Max Planck Society, which is funded by the German state.

"(Russian) colleagues at the Northeast Science Station try to keep the station running," Hergersberg said. He declined to say how much funding was withheld.

Reuters spoke with more than two dozen scientists about the impact of the Ukraine conflict on Russian science. Many expressed concern about its future after tens of millions of dollars in Western funding for Russian science has been suspended in the wake of European sanctions on Moscow.

Hundreds of partnerships between Russian and Western institutions have been paused if not canceled altogether, the scientists said, as the invasion has unraveled years spent building international cooperation following the Soviet Union's 1991 collapse.

Many communication channels are closed and research trips have been postponed indefinitely.

The projects affected by the suspension of Western assistance include the construction of high-tech research facilities in Russia, such as an ion collider and a neutron reactor for which Europe had pledged 25 million euros ($27.4 million).

Such technology would unlock a generation of research that could contribute to everything from fundamental physics to the development of new materials, fuels and pharmaceuticals, scientists said.

Another 15 million-euro ($16.7 million) contribution toward designing low-carbon materials and battery technologies needed in the energy transition to combat climate change has also been frozen, after the European Union halted all cooperation with Russian entities last month.

"Emotionally, I can understand this suspension," said Dmitry Shchepashchenko, a Russian environmental scientist who studies global forest cover and has been affiliated with the International Institute for Applied Systems Analysis in Austria since 2007.

But for science overall, he said: "This is a lose-lose solution. Global issues like climate change and biodiversity ... can hardly be solved without Russian territory [and] the expertise of Russian scientists."

FROZEN FINANCES

When the Soviet Union broke apart, Russian spending on science plummeted, and thousands of scientists moved abroad or abandoned their fields altogether.

"We felt as scientists that our work was not appreciated," said permafrost scientist Vladimir Romanovksy, who moved his work to Fairbanks, Alaska, in the 1990s. "There was practically no funding, especially for field work."

Russian funding has since improved, but remains far below that of the West. In 2019, Russia spent 1% of its GDP on research and development — or about $39 billion, adjusted for currency and price variation — according to the Organisation for Economic Co-operation and Development (OECD).

Most of that money has been spent in physical science fields, such as space technology and nuclear energy.

By comparison, Germany, Japan and the United States each spend around 3% of their respective GDPs. For the United States, that amounted to $612 billion in 2019.

Russian science got a boost, though, from partnerships on projects with scientists abroad. Russia and the United States, for example, led the international consortium that launched the International Space Station in 1998.

The head of Russia's space agency, Roscosmos, said this month it would suspend its participation in the space station until sanctions tied to the Ukraine invasion are lifted.

Russian scientists also helped build the Large Hadron Collider, the world's most powerful particle accelerator, at the European Organization for Nuclear Research in Switzerland, known as CERN. In 2012, the collider made the breakthrough discovery of the elusive Higgs boson, which until then had only been theorized.

Scientific camaraderie with Europe continued uninterrupted after Russia annexed Crimea from Ukraine in 2014. But CERN's governing council announced last month it was suspending any new collaboration with Russia.

Germany alone has given some 110 million euros ($122 million) toward more than 300 German-Russian projects over the last three years. A further 12.6 million euros ($14 million) in EU funding was awarded to Russian organisations for another 18 projects focusing on everything from Arctic climate monitoring to infectious animal diseases.

Chemist Pavel Troshin recently won Russian state funding for his part in a Russian-German effort to develop next-generation solar cells to power communication satellites. But, with the German side now suspended, the project is up in the air.

Joint projects "are supposed to be done for the benefit of all the world, and cutting out Russian scientists ... is really counter-productive," said Troshin, who works at Russia's Institute for Problems of Chemical Physics.

"I would never expect something like this. It's shocking to me. I'm upset very much."

ARCTIC BLACKOUT

Among the more urgent research efforts on hold are projects to study climate change in the Russian Arctic.

"Two-thirds of the permafrost region is in Russia, so data from there is critical,” said Northern Arizona University ecologist Ted Schuur of the Permafrost Carbon Network.

"If you cut off your view of changing permafrost in Russia, you're really cutting off our understanding of global changes to permafrost."

That's alarming for scientists as global warming thaws the long-frozen ground that holds an estimated 1.5 trillion metric tons of organic carbon – twice the amount already in the atmosphere today.

As permafrost thaws, organic material locked within the ice decays and releases more planet-warming gases like methane and carbon dioxide. Scientists fear that such emissions could cause climate change to spiral out of control.

Scientists can use satellites to monitor landscape changes due to thaw, but can't pick up what's happening below ground, which requires on-site research, Schuur said.

Russian scientists have collected and shared permafrost field data for years, but Western researchers aren't sure if those communication channels will remain open. Those datasets were also patchy, due to limited funding to cover the vast region.

Arctic ecologist Sue Natali, at U.S. Woodwell Climate Research Center, said her project's plans for boosting Russian monitoring capability is on hold.

"Instrumentation that was supposed to go out this year has been halted," she said, as her colleagues' travel plans have been canceled.

The U.S. government has issued no clear directive on interacting with Russian institutions, contrary to the European stance.

A State Department spokesperson told Reuters: "We do not hold the people of Russia responsible [for the conflict], and believe that continued direct engagement with the Russian people is essential – including in science and technology fields."

SCIENCE AS COLLATERAL DAMAGE

Projects under the Russian Science Foundation's state-funded 2021 budget of 22.9 billion rubles ($213 million) had relied on partnerships with India, China, Japan, France, Austria, and Germany, among others.

A spokesperson did not answer Reuters questions about how the halt in European collaboration would affect its work, saying only that the foundation would "continue to support leading teams of researchers and their research projects."

European scientists had been helping to build Russian research sites including the neutron reactor and the ion collider near St. Petersburg, said Martin Sandhop, a coordinator on this EU-funded effort called CremlinPlus.

The facilities would help to drive research in fields like high-energy physics, biochemistry and materials science.

But plans for a 25-million-euro project extension are now suspended and Sandhop's team is redirecting experts and equipment toward European institutions.

Cremlin's neutron detectors needed for the planned reactor, for example, are now going to a facility in Lund, Sweden.

Even if Russia manages to complete the expansion works, it's unclear how valuable the work will be without the suite of tools at Western institutions to analyse the data.

Physicist Efim Khazanov at the Institute of Applied Physics in Nizhny Novgorod, near Moscow, said not having access to European equipment would hurt his work using a high-energy laser to study topics such as the structure of spacetime in a vacuum, which could expand our understanding of the universe.

Khazanov was among thousands of Russian scientists who signed an open letter, posted on the independent online science publication Troitskiy Variant, saying Russia had "doomed itself to international isolation" with its invasion of Ukraine.

Many Russian scientists also fled the country, said Alexander Sergeev, head of the Russian Academy of Sciences, according to Interfax state news agency.

The protest letter was temporarily removed from the site after Russia passed a law March 4 criminalizing "fake news" on the Ukraine campaign.

That day, a letter was published on the state Russian Rectors' Union website in support of Russia's invasion and signed by more than 300 leading scientists, who have since been suspended from European University Association membership.

While foreign funding represents just a small part of Russia's scientific spending, its scientists relied on that money to keep projects and careers afloat.

"Those joint research grants were helping a lot of Russians," lamented Russian geographer Dmitry Streletskiy, at George Washington University in Washington, D.C. "I'm just surprised the EU is targeting scientists, which is not the right crowd to target."

https://www.nasdaq.com/articles/insight-ukraine-conflict-hurts-russian-science-as-west-pulls-funding

AACR: Adagene Data Demonstrates First and Best-In-Class Potential for Differentiated Preclinical Antibody

 Adagene Inc. announced preclinical data showcasing the potential first/best-in-class profile of new antibody candidates. Data are being presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place in New Orleans, Louisiana from April 8 to 13, 2022. Key takeaways from the four posters include: ADG206, an anti-CD137 agonistic POWERbody™ with tailor-made efficacy and safety profiles by strong crosslinking and tumor selective activation for single agent and combinational cancer immunotherapy (#2868): This masked, IgG1 Fc-engineered anti-CD137 POWERbody combines conditional activation in the tumor microenvironment with strong agonistic activity through heightened Fc?R-mediated crosslinking for therapeutic potential in either single agent or combination regimens; Preclinical data demonstrated that ADG206 was well tolerated and had robust anti-tumor activity as a single agent in multiple tumor models, with 4-fold stronger anti-CD137 agonistic activity of its activated form than a benchmark antibody in development (analog of urelumab) for T cell co-activation; ADG206 also demonstrated enhanced anti-tumor activity in combination with other checkpoint inhibitors, including anti-PD-1 or anti-CTLA-4 therapy; Adagene is preparing to submit an IND or equivalent filing for ADG206 during 2022. ADG153-G1 SAFEbody, a differentiated masked anti-CD47 antibody of IgG1 subclass, demonstrates in vivo anti-tumor activity consistent with enhanced ADCC/ADCP effects and significantly reduced RBC-related and antigen sink liabilities“ (#4257): This masked anti-CD47 IgG1 SAFEbody is differentiated by its strong antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity designed to realize the full potential of anti-CD47 therapy for both hematologic and solid tumor indications; Preclinical data demonstrated that ADG153 IgG1 was well tolerated, did not induce human hemagglutination and significantly reduced anemia-related and antigen sink liabilities. In particular, ADG153 IgG1 at a 10 mg/kg dose demonstrated only an 8% decrease in red blood cell counts, compared to a 49 percent decrease with a benchmark antibody which is in IgG4 format (analogue of magrolimab); Results also showed that ADG153 IgG1 demonstrated greater anti-tumor activity than the benchmark; Adagene is preparing to submit an IND or equivalent filing for ADG153 during 2022; ADG138, A Novel HER2×CD3 POWERbody™ Integrating Bispecific TCE with Precision Masking to Control Cytokine Release Syndrome and On-Target Off-Tumor Toxicity for Single Agent and Combination Therapies in HER2-Expressing Solid Tumors (#2869): This novel HER2xCD3 POWERbody is masked on both arms with an impressively high therapeutic index relative to its parental non-masked TCE in both HER2 high and low expressing solid tumors, supporting its development for HER2-expressing solid tumors as a single agent and in combination with other immune modulating agents; Preclinical data demonstrated the excellent safety profile of ADG138, including 100-fold greater reduction in cytokine release compared to its parental TCE; Results showed that ADG138 has potent anti-tumor activity in HER2 high and low expressing tumors, as well as resistant/refractory tumors, relative to a benchmark antibody (DS-8201, a HER2 targeting antibody drug conjugate commercially available in specific indications). ADG138 also had synergistic anti-tumor activity in HER2 positive tumors when combined with anti-CD137 or anti-PD-1 therapy, or tumor targeted CD28 bispecific antibody; ADG138 is currently in IND-enabling studies. Tumor-targeted CD28 bispecific POWERbody™ for safe and synergistic T cell-mediated immunotherapy (#2888); CD28 bispecific POWERbody TCEs exhibit enormous potential to fulfill the promises of safe and durable T cell-mediated synergistic immunotherapies when combined with CD3 bispecific POWERbody TCEs and/or checkpoint inhibitors; Enabled by Adagene’s suite of antibody platform technologies, preclinical data demonstrated the potential to mitigate the serious safety concerns of CD28 activation and make custom designed antibodies targeting a highly conserved epitope with broad species reactivity; Multiple tumor associated antigen (TAA)xCD28 POWERbodies are in progress, such as B7-H3xCD28 and HER2xCD28, which can also be combined with the company’s CD3 TCEs to achieve safe, powerful and durable immunotherapy for solid tumors through combination of the fundamental mechanisms and pathways across the cancer immunity cycle.

https://www.marketscreener.com/quote/stock/ADAGENE-INC-118740050/news/Adagene-Inc-Presents-Data-Demonstrating-First-and-Best-In-Class-Potential-for-Differentiated-Precli-40017145/

AACR: Senti fine-tunes cytokines to boost CAR-NK cell therapy for solid cancers

 Senti Bio is perhaps best known for logic-gated gene circuits to control the therapeutic activity of cell and gene therapies. But the California biotech now has early data showing its platform has more tricks up its sleeve.

Developing CAR-NK cells for solid tumors, Senti created a novel calibrated release technology to fine-tune the signaling of cytokines to further boost the function of cell therapy in solid tumors. CAR-NK cells armed with interleukin-15 (IL-15) based on the new gene circuit showed potent antitumor activity and persistence in mice as well as activation of other immune cells, according to data presented at the American Association for Cancer Research.

Senti is already applying the calibrated release technology to several pipeline products including SENTI-301 and SENTI-401, designed for liver cancer and colorectal cancer, respectively.

Solid tumors have proven difficult for cell therapies to target because the tumors lack unique antigens that can help immune cells differentiate them from healthy tissues. And the tumor microenvironment can be hostile for immune cells to survive.

Senti is solving the cancer identification problem with logic-gated gene circuits, which can recognize more than one antigen and then activate or block the therapy accordingly. To improve the CAR-NK cells’ potency, the company is turning to interleukins, adopting a common approach though slightly differently than other cell therapy developers, Senti Bio CEO Tim Lu, M.D., Ph.D., said in an interview with Fierce Biotech Research.

“There are two aspects we’re trying to optimize,” Lu said, “one aspect is how do we make the NK cells themselves as potent as possible, and the second is how do we use the NK cells to stimulate the surrounding tumor microenvironment?”

Once produced, a cytokine is tethered to the cell membrane. Senti added a cleavable linker, which can be cut by a cell surface protease at a pace of Senti’s design, thereby allowing for a controlled release of the cytokine into the surrounding tumor site. That way, the therapy can get optimal stimulation of the CAR-NK cells themselves by the membrane-bound cytokines as well as engagement with the local immune community, Lu explained.

Senti picked IL-15 because it’s a well-established booster for NK cells, Lu said. In lab dishes, CAR-NK cells armed with the novel IL-15, or crIL-15, showed improved expansion and survival compared with those carrying normal IL-15.

In a serial killing assay, where the immune cells were periodically rechallenged with new cancer cells over 196 hours, the crIL-15 CAR-NK cells were able to continue to kill cancer cells at all three time points, whereas CAR-NK cells with typical IL-15 and unengineered NK cells only controlled tumor cells at the initial point.

The crIL-15 CAR-NK cells also showed increased persistence and better anti-tumor activity in mice, with tumor shrinkage in 62% of the animals, whereas CAR-NK cells alone failed to shrink tumors.

Separately, Senti also showed that the combination of IL-15 and IL-21 led to a synergistic effect, as the multi-armed NK cells could live longer in petri dishes than those armed with IL-15 alone. CAR-NK cells armed with both IL-15 and IL-21 cleared over 90% of tumor cells in lab dishes, whereas IL-15 alone killed about 70%.

Lu noted that IL-21 is just the first cytokine Senti is presenting alongside IL-15. The company is running systematic screens to see which cytokines could work with IL-15 in different settings. For SENTI-301, for instance, Senti is pairing IL-15 with IL-12.

“We want to use the NK cells not just directly like a soldier to kill the tumor cells but also as a factory to produce other cytokines,” Lu said. “We’re typically looking at multiple cytokines together because we think that has the best chance of amplifying the effect.”

Senti is currently in the process of a SPAC merger with Dynamics Special Purpose, which has former Illumina executive Mostafa Ronaghi, Ph.D., as CEO and Robert Langer as chief scientific adviser. The deal values Senti at $601 million.

The 2018 Fierce Biotech Fierce 15 winner aims to file first-in-human clinical trial applications for its two lead programs, SENTI-202 for acute myeloid leukemia and SENTI-301, next year. The designs of those two programs are almost complete, Lu said, and the company is moving into the manufacturing process.

Besides being able to adjust the release of cytokines, Senti has devised another gene circuit, called the “regulator dial,” to control how much of the cytokines are produced, Lu said. It involves an FDA-approved oral small molecule drug to trigger the production.

“We’re not just a logic gate company, we’re not just a cytokine company,” Lu said. “The key thing that we’ve developed is how do we put these genes together and how do we get them with each other properly … and don’t interfere with each other. That’s the future.”

https://www.fiercebiotech.com/research/senti-bio-fine-tunes-cytokines-gene-circuit-boost-car-nk-cell-therapy-solid-cancers