At Rezvani Lab in MD Anderson Cancer Center, scientists train immune cells to fight cancer. Photo via Getty Images

Replay, a genome-writing company headquartered in San Diego, has announced that its first patient has been dosed with an engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma.

What does that have to do with Houston? Last year, Replay incorporated a first-in-class engineered TCR-NK cell therapy product company, Syena, using technology developed by Dr. Katy Rezvani at The University of Texas MD Anderson Cancer Center.

Rezvani, a professor of stem cell transplantation and cellular therapy, is the force behind MD Anderson’s Rezvani Lab, a group of 55 people, all focused on harnessing natural killer cells to combat cancer.

“Everybody thinks that the immune system is fighting viruses and infections, but I feel our immune system is capable of recognizing and killing abnormal cells or cells that are becoming cancerous and they're very powerful. This whole field of immunotherapy really refers to the power of the immune system,” Rezvani tells InnovationMap.

Dr. Katy Rezvani is a professor of stem cell transplantation and cellular therapy and the force behind MD Anderson’s Rezvani Lab, which is focused on harnessing natural killer cells to combat cancer. Photo via mdanderson.org

At Rezvani Lab, scientists train immune cells to fight cancer. While cancer drugs like chemotherapy are still the norm, immunotherapy has gained ground, led by Houston research, including the work of Nobel laureate Jim Allison. The harnessed cells are taught to attack cancerous cells, while ignoring healthy ones, says Rezvani. “We’re turning them into heat-seeking missiles,” she explains.

However, there must be a beacon to signal to those “missiles” that there is something to attack. Much of the field has used chimeric antigen receptors (CARs) to achieve that. But they have limitations.

“CARs can only recognize beacons that sit on the surface of the tumor cells,” Rezvani says. “So basically, it's like the tumor cell has to have a hat on it.”

She says that this usually means that the targets that send off a signal are relatively limited, mostly blood cancers. Using T cell receptors (TCRs) may be able to open up the field to look beyond the “hat.” In other words, TCRs can peer inside cells and see what differentiates a tumor cell from healthy cells. With Replay, Rezvani Lab has developed a first-in-class and first-in-human approach of engineering natural killer cells to express the TCR.

There are six different FDA-approved products that use CAR-T cells, but Rezvani says that her TCR-NK-based technology, though still in its early phases, shows great promise.

“We could use it to target many different types of antigens, many different types of cancers, especially solid tumors," she explains. "These cell therapies have a lot of potential — we call them living drugs… It's not like chemotherapy where you have to keep giving different multiple cycles, these cells are very long lived.”

Rezvani, who started her career in London, says that Houston has been instrumental in the success of her lab.

“There are so many opportunities because we have access to some of the most brilliant minds in research,” Rezvani says. “We have some of the best clinicians in the world. We have patients who come to us who are willing to participate in our clinical trials — really put their trust in us — and are committed and want to participate in these clinical studies.”

The role of funding also plays a part. As Rezvani admitted, bringing a new technology to the market is expensive. The philanthropists who help support trials can’t be forgotten among Houston’s finest.

Whether or not Syena produces the first TCR-NK product on the market, Rezvani is enthusiastic and hopeful for the future of her patients.

“The field of immunotherapy is really expanding, the field of cell therapies is expanding, and there is so much promise,” she says. “The promise of AI, big data, all the engineering tools that we have available, the promise of CRISPR — all of that is going to bring what we've learned from biology, from basic science, together to help us make the cell therapies that are going to be safe and and also very effective for our patients.”

A Houston health care company received the green light from the FDA to advance a treatment that's targeting a deadly cancer. Photo via Getty Images

Houston immunotherapy company achieves FDA designation for cancer-fighting vaccine

got the green light

The FDA has granted a Houston-based company a Fast Track designation.

Diakonos Oncology Corp. is a clinical-stage immuno-oncology company that has developed a unique dendritic cell vaccine, DOC1021. The vaccine targets glioblastoma multiforme (GBM), the most common and most lethal malignant brain tumor in adults. The aggressive tumors come with a life expectancy of about 15 months following diagnosis. About 7 percent of those diagnosed survive five years, while the 10-year outlook only sees a one-percent survival rate.

“The FDA’s decision acknowledges the potential of this new treatment approach for a very challenging disease,” Diakonos CEO Mike Wicks says in a press release. “Our protocol represents a first for cancer immunotherapy and could be viable for many types of cancers beyond GBM.”

FDA Fast Track designations are intended to expedite the haste with which drugs with early clinical promise are reviewed, likely taking them to market faster.

DOC1021 uses the body’s natural anti-viral immune response to fight GBM. The vaccine mimics viral infection with the patient’s cancer markers. Essentially, DOC1021 uses the body’s own natural ability to detect and eliminate infected cells.

The technology uses dendritic cells, white blood cells that are able to perceive threats, to its advantage. The unique cancer markers are loaded both internally and externally into the immune cells, just as they would simultaneously occur in a viral infection. The individualized treatment is administered through three precise injections that target deep cervical lymph node chains. By dosing this way, the immune responses are directed straight to the central nervous system.

The results have spoken for themselves: All of the patients who have tried the treatment have exceeded survival expectations. And just as importantly, DOC1021 appears to be extremely safe. No serious adverse effects have been reported.

“Because Phase I clinical trials are generally not statistically powered to demonstrate efficacy, detection of a statistically significant efficacy signal is very promising,” says William Decker, associate professor of immunology at Baylor College of Medicine and inventor of the DOC1021 technology.

The Phase 1 open-label trial of DOC1021 (NCT04552886) is currently taking place at both the University of Texas Health Science Center in Houston and at the MD Anderson Cancer Center at Cooper University Health Care in Camden, NJ. The trial is expected to complete this year.

7 Hills Pharma, an innovative immunotherapy company, was awarded a $13.5 million grant from the Cancer Prevention and Research Institute of Texas. Photo via Getty Images

Houston immunotherapy company to use $13.5M grant to further develop cancer treatments

future of pharma

Between Bangalore and Chennai in the Indian state of Andhra Pradesh, you’ll find the town of Tirupati. It’s home to seven peaks that host a Hindu temple complex devoted to a form of Vishnu, Venkateshvara. It is also the region from which Upendra Marathi originally hails. It’s where his father, and many other family members, attended medical school.

“My father’s first job was to take care of the pilgrims,” recalls Marathi.

It's only natural that his groundbreaking Houston company would be named 7 Hills Pharma.

“That sort of selflessness and giving back, I wanted to embody it in the name of the company,” Marathi says.

Now, 7 Hills Pharma is announcing that last month, it was awarded a $13.5 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT). That’s on top of more than $13 million in NIH grants, making the company the second largest recipient of SBIR/STTR grants in Texas.

Launched in 2016, 7 Hills Pharma is working to develop drugs that can overcome the all-too-common problem of immunotherapy resistance. Thanks to the Nobel Prize-winning work of Jim Allison in the realm of immuno-oncology, the field was “very hot” at the time, says Marathi, particularly in Houston.

So what has 7 Hills developed? Oral small molecules that activate integrins — the receptors that allow cells to bind to one another — allowing for the cell-to-cell interactions that create a successful immune response to immune checkpoint inhibitors such as Yervoy. In other words, they have created capsules that increase the effectiveness of drugs that allow the body’s own immune response to fight cancers.

But that’s not all. Tests have shown that the same discovery, called alintegimod, can also augment the effectiveness of vaccines. The pill, which co-founder and co-inventor Peter Vanderslice calls “a beautiful way to amplify the vaccines,” can potentially be applied to anything from influenza to coronavirus.

Their greatest challenge, says Vanderslice, is the very fact that the technology is so novel.

“Most large pharmas are very risk averse,” he explains. “They only want to do ‘me-too’ kinds of drugs.”

7 Hills Pharma is the third company Marathi, both a PhD and an MBA, has helped to found based on technology he co-invented. Vanderslice is director of the molecular cardiology research laboratories at The Texas Heart Institute.

“It’s very much a homegrown company,” Marathi says.

And a small one, at least for now. Working out of JLabs@TMC, the full-time team is currently just Marathi and Siddhartha De, the senior director of development. Marathi convinced De to transplant himself and his family from India for the purpose of assisting 7 Hills with preparing its drugs for clinical readiness.

The CPRIT funds will allow 7 Hills Pharma to hire several long-time team members full-time and with benefits.

“The bringing of talent and bringing of technology to TMC and what was born at Texas Heart Institute is rather remarkable,” says Rob Bent, the company’s director of operations.

The next step for 7 Hills Pharma is a Phase Ib/IIa clinical trial in patients with treatment-resistant solid tumors. And the team just finalized the deck that will help raise another $10 million to $250 million in the company’s series A. And hopefully sooner rather than later, a new set of medical pilgrims will be thanking 7 Hill Pharma for its care.

A UH professor is fighting cancer with a newly created virus that targets the bad cells and leaves the good ones alone. Photo via Getty Images

University of Houston researchers snag $1.8M to develop cancer-fighting virus

immunotherapy innovation

Viruses attack human cells, and that's usually a bad thing — some Houston researchers have received fresh funding to develop and use the evil powers of viruses for good.

The developing cancer treatment is called oncolytic virotherapy and has risen in popularity among immunotherapy research. The viruses can kill cancer cells while being ineffective to surrounding cells and tissue. Basically, the virus targets the bad guys by "activating an antitumor immune response made of immune cells such as natural killer (NK) cells," according to a news release from the University of Houston.

However exciting this rising OV treatment seems, the early stage development is far from perfect. Shaun Zhang, director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston, is hoping his work will help improve OV treatment and make it more effective.

“We have developed a novel strategy that not only can prevent NK cells from clearing the administered oncolytic virus, but also goes one step further by guiding them to attack tumor cells. We took an entirely different approach to create this oncolytic virotherapy by deleting a region of the gene which has been shown to activate the signaling pathway that enables the virus to replicate in normal cells,” Zhang says in the release.

Zhang, who is also a M.D. Anderson professor in the Department of Biology & Biochemistry, has received a $1.8 million grant from the National Institutes of Health to continue his work.

Zhang and his team are specifically creating a new OV — called FusOn-H2 and based on the Herpes simplex 2 virus.

“Our recent studies showed that arming FusOn-H2 with a chimeric NK engager (C-NK-E) that can engage the infiltrated natural killer cells with tumor cells could significantly enhance the effectiveness of this virotherapy,” he says. “Most importantly, we observed that tumor destruction by the joint effect of the direct oncolysis and the engaged NK cells led to a measurable elicitation of neoantigen-specific antitumor immunity.”

Shaun Zhang is the director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston and M.D. Anderson professor in the Department of Biology & Biochemistry. Image via UH.edu

Houston's Nobel Prize winner, Jim Allison, is the star of Breakthrough, which premieres on Independent Lens at 9 pm Monday, April 27, on PBS, PBS.org, and the PBS Video App. Photo via SXSW.com

Documentary featuring Houston Nobel Prize winner to air on PBS

to-watch list

Not all heroes wear capes. In fact, our current coronavirus heroes are donning face masks as they save lives. One local health care hero has a different disease as his enemy, and you'll soon be able to stream his story.

Dr. James "Jim" Allison won the 2018 Nobel Prize in Physiology or Medicine for his work in battling cancer by treating the immune system — rather than the tumor. Allison, who is the chair of Immunology and executive director of the Immunotherapy Platform at MD Anderson Cancer Center, has quietly and often, singularly, waged war with cancer utilizing this unique approach.

The soft-spoken trailblazer is the subject of an award-winning documentary, Jim Allison: Breakthrough, which will air on PBS and its streaming channels on Monday, April 27 at 9 pm (check local listings for channel information). Lauded as "the most cheering film of the year" by the Washington Post, the film follows Allison's personal journey to defeat cancer, inspired and driven by the disease killed his mother.

Breakthrough is narrated by Woody Harrelson and features music by Willie Nelson, adding a distinct hint of Texana. (The film was a star at 2019's South by Southwest film festival.) The documentary charts Alice, Texas native as he enrolls at the University of Texas, Austin and ultimately, cultivates an interest in T cells and the immune system — and begins to frequent Austin's legendary music scene. Fascinated by the immune system's power to protect the body from disease, Allison's research soon focuses on how it can be used to treat cancer.

Viewers will find Allison charming, humble, and entertaining: the venerable doctor is also an accomplished blues harmonica player. Director Bill Haney weaves Allison's personal story with the medical case of Sharon Belvin, a patient diagnosed with melanoma in 2004 who soon enrolled in Allison's clinical trials. Belvin has since been entirely cancer-free, according to press materials.

"We are facing a global health challenge that knows no boundaries or race or religion, and we are all relying on gifted and passionate scientists and healthcare workers to contain and ultimately beat this thing," said Haney, in a statement. "Jim Allison and the unrelenting scientists like him are my heroes – and I'll bet they become yours!"

Jim Allison: Breakthrough premieres on Independent Lens at 9 pm Monday, April 27, on PBS, PBS.org, and the PBS Video App.

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This article originally ran on CultureMap.

Houston researchers are hard at work in the lab to progress medical advancements at the bedside. Getty Images

These 3 medical innovations are ones to watch in Houston

Research roundup

Every day, important research is being completed under the roofs of Houston medical institutions. From immunotherapy to complex studies on how a memory is made, Houston researchers are discovering and analyzing important aspects of the future of medicine.

Here are three research projects currently being conducted around town.

University of Houston's potential solution to sickle cell disease

Vassiliy Lubchenko is a University of Houston associate professor of chemistry. Courtesy of UH

For the most part, sickle cells have been a mystery to scientists, but one University of Houston professor has recently reported a new finding on how sickle cells are formed — enlightening the medical community with hopes that better understanding the disease may lead to prevention.

Vassiliy Lubchenko, UH associate professor of chemistry, shared his new finding in Nature Communications. He reports that "droplets of liquid, enriched in hemoglobin, form clusters inside some red blood cells when two hemoglobin molecules form a bond — but only briefly, for one thousandth of a second or so," reads a release from UH.

In sickle cell disease, or anemia, red blood cells are crescent shaped and don't flow as easily through narrow blood vessels. The misshapen cells are caused by abnormal hemoglobin molecules that line up into stiff filaments inside red blood cells. Those filaments grow when the protein forms tiny droplets called mesoscopic.

"Though relatively small in number, the mesoscopic clusters pack a punch," says Lubchenko in the release. "They serve as essential nucleation, or growth, centers for things like sickle cell anemia fibers or protein crystals. The sickle cell fibers are the cause of a debilitating and painful disease, while making protein crystals remains to this day the most important tool for structural biologists."

Lubchenko conclusion is that the key to prevent sickle cell disease is to is to stop the formation of the initial clusters so fibers aren't able to grow out of them.

Baylor College of Medicine's immunotherapy research in breast cancer

science-Digital Composite Image Of Male Scientist Experimenting In Laboratory

Baylor College of Medicine researchers are looking into the complexities of immune cells in breast cancer. Getty Images

Baylor College of Medicine researchers are leading an initiative to figure out the potential effect of immunotherapy on different types of breast cancers. Their report is featured in Nature Cell Biology.

The scientists zoned in on two types of immune cells — neutrophils and macrophages — and they found frequency differed in a way that indicated potential roles in immunotherapy.

"Focusing on neutrophils and macrophages, we investigated whether different tumors had the same immune cell composition and whether seemingly similar immune components played the same role in tumor growth. Importantly, we wanted to find out whether differences in immune cell composition contributed to the tumors' responses to immunotherapy," says Dr. Xiang 'Shawn' Zhang, professor at the Lester and Sue Smith Breast Center and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, in a news release.

Further exploring the discrepancies between the immune cells and the role they play in tumor growth will help better understand immunotherapy's potential in certain types of breast cancer.

"These findings are just the beginning. They highlight the need to investigate these two cellular types deeper. Under the name 'macrophages' there are many different cellular subtypes and the same stands for neutrophils," Zhang says. "We need to identify at single cell level which subtypes favor and which ones disrupt tumor growth taking also into consideration tumor heterogeneity as both are relevant to therapy."

Rice University, UTHeath, and UH's memory-making study

Researchers from all corners of Houston are diving into how memories are made. Courtesy of Rice University

When you make a memory, your brain cells structurally change. Through a multi-institutional study with researchers from UH, Rice University, and the University of Texas Health Science Center at Houston, we now know more about the way memories are made.

When forming memories, three moving parts work together in the human brain — a binding protein, a structural protein and calcium — to allow for electrical signals to enter neural cells and change the molecular structures in cognition. The scientists compared notes on how on that binding protein works.

The team's study was published in the Proceedings of the National Academy of Sciences. Peter Wolynes, a theoretical physicist at Rice, UH physicist Margaret Cheung, and UTHealth neurobiologist Neal Waxham worked together to understand the complex process memories experience in the process of being made.

"This is one of the most interesting problems in neuroscience: How do short-term chemical changes lead to something long term, like memory?" Waxham says in a release from Rice. "I think one of the most interesting contributions we make is to capture how the system takes changes that happen in milliseconds to seconds and builds something that can outlive the initial signal."

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Houston family's $20M donation drives neurodegeneration research

big impact

Neurodegeneration is one of the cruelest ways to age, but one Houston family is sharing its wealth to invigorate research with the goal of eradicating diseases like Alzheimer’s.

This month, Laurence Belfer announced that his family, led by oil tycoon Robert Belfer, had donated an additional $20 million to the Belfer Neurodegeneration Consortium, a multi-institutional initiative that targets the study and treatment of Alzheimer’s disease.

This latest sum brings the family’s donations to BNDC to $53.5 million over a little more than a decade. The Belfer family’s recent donation will be matched by institutional philanthropic efforts, meaning BNDC will actually be $40 million richer.

BNDC was formed in 2012 to help scientists gain stronger awareness of neurodegenerative disease biology and its potential treatments. It incorporates not only The University of Texas MD Anderson Cancer Center, but also Baylor College of Medicine, Massachusetts Institute of Technology (MIT) and Icahn School of Medicine at Mount Sinai.

It is the BNDC’s lofty objective to develop five new drugs for Alzheimer’s disease and related disorders over the next 10 years, with two treatments to demonstrate clinical efficacy.

“Our goal is ambitious, but having access to the vast clinical trial expertise at MD Anderson ensures our therapeutics can improve the lives of patients everywhere,” BNDC Executive Director Jim Ray says in a press release. “The key elements for success are in place: a powerful research model, a winning collaborative team and a robust translational pipeline, all in the right place at the right time.”

It may seem out of place that this research is happening at MD Anderson, but scientists are delving into the intersection between cancer and neurological disease through the hospital’s Cancer Neuroscience Program.

“Since the consortium was formed, we have made tremendous progress in our understanding of the molecular and genetic basis of neurodegenerative diseases and in translating those findings into effective targeted drugs and diagnostics for patients,” Ray continues. “Yet, we still have more work to do. Alzheimer's disease is already the most expensive disease in the United States. As our population continues to age, addressing quality-of-life issues and other challenges of treating and living with age-associated diseases must become a priority.”

And for the magnanimous Belfer family, it already is.

3 Houston innovators to know this week

who's who

Editor's note: Every week, I introduce you to a handful of Houston innovators to know recently making headlines with news of innovative technology, investment activity, and more. This week's batch includes a podcast with the founder of a new venture firm, a former astronaut and recent award recipient, and a health care innovator with fresh funding.

Zach Ellis, founder and managing partner of South Loop Ventures

Zach Ellis explains on the Houston Innovators Podcast that South Loop Ventures plans to invest in promising companies from across the country and bring them into Houston's ecosystem to grow and scale. Photo via LinkedIn

Houston has a lot of the right ingredients for commercialization and scaling up companies, so when Zach Ellis moved to town to stand up a venture capital firm that made investments in diverse founders, he decided to go about it in an innovative way.

South Loop Ventures, which Ellis launched two years ago, invests in pre-seed and seed-stage startups across health care, climatetech, aerospace, sports, and fintech. While the first handful of investments, which have already been made, are into Houston-based companies, Ellis explains on the Houston Innovators Podcast that the firm plans to invest in promising companies from across the country and bring them into Houston's ecosystem to grow and scale.

"Any investor wants to feel like they are looking at the best possible investment opportunities in which to deploy capital," Ellis says on the show. "So that's reason No. 1 to cast your net as widely as possible.

"At the same time, you want to give any investment that you make greatest chances of success," he continues. "The biggest factor of success outside of the team and the capital you give them, is the customers that they can call upon. In bringing targeted companies to Houston or connecting them with Houston, you introduce the opportunity for them to achieve rapid scale and work with world-class partners very efficiently." Read more.


Toby R. Hamilton, founder and CEO of Hamilton Health Box

Dr. Toby Hamilton has secured $10 million to grow his company. Photo via tmc.edu

A Houston company that is working on a value-based model for primary care has fresh funding to support its mission.

Hamilton Health Box announced the completion of a $10 million series A funding round led by 1588 Ventures with participation from Memorial Hermann Health System, Impact Ventures by Johnson & Johnson Foundation, Texas Medical Center Venture Fund, and the Sullivan Brothers.

The company, founded in 2019 by Dr. Toby R. Hamilton, will use the funding to fuel its expansion into rural areas to help assist those living in Health Professional Shortage Areas, or HPSAs. Read more.

Ellen Ochoa, former astronaut and center director at the NASA's Johnson Space Center

Ellen Ochoa was recognized for her leadership at NASA Johnson and for being the first Hispanic woman in space. Photo via NASA

Two astronauts recently received Presidential Medals of Freedom from President Joe Biden for their leadership in space.

Ellen Ochoa, the former center director and astronaut at the NASA's Johnson Space Center in Houston, and Jane Rigby, senior project scientist for NASA’s James Webb Space Telescope, were honored at the White House on May 3.

Ochoa spent 30 years with NASA, which included being the 11th director of JSC, deputy center director of JSC, and director of Flight Crew Operations. She served on the nine-day STS-56 mission aboard the space shuttle Discovery in 1993, and became the first Hispanic woman in space. She flew four more times to space with STS-66, STS-96, STS-110, and more.

“I’m so grateful for all my amazing NASA colleagues who shared my career journey with me,” Ochoa says in a NASA news release. Read more.

Houston health care institutions receive $22M to attract top recruits

coming to Hou

Houston’s Baylor College of Medicine has received a total of $12 million in grants from the Cancer Prevention & Research Institute of Texas to attract two prominent researchers.

The two grants, which are $6 million each, are earmarked for recruitment of Thomas Milner and Radek Skoda. The Cancer Prevention & Research Institute of Texas (CPRIT) announced the grants May 14.

Milner, an expert in photomedicine for surgery and diagnostics, is a professor of surgery and biomedical engineering at the Beckman Laser Institute & Medical Clinic at the University of California, Irvine and the university’s Chao Family Comprehensive Cancer Center

In 2013, Milner was named Inventor of the Year by the University of Texas at Austin. At the time, he was a professor of biomedical engineering at UT. One of his major achievements is co-development of the MasSpec Pen, a handheld device that identifies cancerous tissue within 10 seconds during surgical procedures.

Skoda is a professor of molecular medicine in the Department of Biomedicine at the University of Basel and the University Hospital Basel, both in Switzerland. He specializes in developing treatments for myeloproliferative neoplasms, which are a group of blood diseases including leukemia.

Other recruitment grants provided by the institute to Houston-area organizations are:

  • $4 million for recruitment of Susan Bullman to the University of Texas M.D. Anderson Cancer Center. She was an assistant professor at Seattle’s Fred Hutchinson Cancer Center, where she studied the connection between microbes and cancer.
  • $4 million for recruitment of Oren Rom to the University of Texas M.D. Anderson Cancer Center. Rom is an assistant professor of pathology and translational pathobiology at Louisiana State University Shreveport.
  • Nearly $2 million for recruitment of Lauren Hagler to conduct RNA cancer biology at Texas A&M University. She is a postdoctoral scholar in biochemistry at Stanford University.

The institute also awarded grants to five companies in the Houston area:

  • $4.7 million to 7 Hills Pharma for development of immunotherapies to treat cancer and prevent infectious diseases.
  • $4.5 million to Indapta Therapeutics for the Phase 1 trial of a cell therapy for treatment of multiple myeloma and non-Hodgkin’s lymphoma.
  • $2.75 million to Bectas Therapeutics for development of antibodies and biomarkers to overcome a type of resistance T-cell checkpoint therapy.
  • $2.69 million to MS Pen Technologies for development of technology that differentiates between normal tissue and cancerous tissue during surgery.
  • $2.58 million to Crossbridge Bio for development of an antibody-drug combination to treat certain solid tumors.