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.”

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.

Three Houston innovators to know this week include Kim Raath of Topl, Gaurav Khandelwal of ChaiOne, and Nobel Prize winner Jim Allison. Courtesy photos

3 Houston innovators to know this week

Who's who

This week's Houston innovators to know include a blockchain expert with insight on how COVID-19 is affecting supply chain, a Houston tech leader with a logistics software solution, and a streamable story on cancer treatment innovation.

Kim Raath, CEO and co-founder of Topl

Photo courtesy of Topl

Amid the negativity the COVID-19 news, one Houston startup had an exciting announcement. It reworked its C-suite and Kim Raath, who just finished Ph.D in statistics and a Master's in economics at Rice University, has transitioned into the CEO role. Raath and her co-founders, James Aman and Chris Georgen, recently convened to re-envision the company's next phase.

"It was definitely a cool experience for us as founders to go through together, but I'm glad that all three of us came out of this excited about what we're doing moving forward," says Raath. Read more.

Gaurav Khandelwal, CEO and founder of ChaiOne

Photo courtesy of ChaiOne

Houston tech company ChaiOne recently announced the soft launch of Velostics, the "slack" for logistics that solve wait times and cash flow challenges in the supply chain and logistics industry. The digital logistics platform is set to aid the struggling supply chain as surging demands stretch suppliers, offering their platform free for 60 days.

"At ChaiOne we have a history of helping Houstonians whenever disaster strikes," says CEO and founder, Gaurav Khandelwal. "We created a disaster connect app during Hurricane Harvey for free that connected people with the resources they need. Velostics by pure happenstance happened to be ready for situations like [the coronavirus] when there's a lot of parties that need to collaborate." Read more.

James Allison, chair of Immunology and executive director of the Immunotherapy Platform at MD Anderson Cancer Center

Jim Allison MD Anderson

Photo courtesy of MD Anderson Cancer Center

In a time when our health care heroes are serving on the front lines of the coronavirus, it's a great reminder of the work they all do round — from the research labs and academic institutions to the patient rooms. Jim Allison, a researcher in immunotherapy for MD Anderson Cancer Center recently took home the Nobel Prize for his work. He went on to be the subject of a documentary that premiered at SXSW last year, and that film will be coming to a TV near you.

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

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.

Jim Allison's groundbreaking work with T cells helped him net the award. Photo courtesy of MD Anderson Cancer Center

Houston scientist wins Nobel Prize for breakthrough cancer treatment

Research Recognition

A University of Texas MD Anderson Cancer Center scientist has been lauded for his cancer research. Jim Allison, Ph.D., was announced as the recipient of the 2018 Nobel Prize in Physiology or Medicine on October 1.

Allison, who is the chair of Immunology and executive director of the Immunotherapy Platform, is the first MD Anderson scientist to receive the world's most coveted award for discoveries in the fields of life sciences and medicine. Allison won for his work in launching an effective new way to attack cancer by treating the immune system rather than the tumor, according to a release.

"I'm honored and humbled to receive this prestigious recognition," Allison says in a statement. "A driving motivation for scientists is simply to push the frontiers of knowledge. I didn't set out to study cancer, but to understand the biology of T cells, these incredible cells to travel our bodies and work to protect us."

Allison shares the award with Tasuku Honjo, M.D., Ph.D., of Kyoto University in Japan. When announcing the honor, the Nobel Assembly of Karolinska Institute in Stockholm noted in a statement that "stimulating the ability of our immune system to attack tumor cells, this year's Nobel Prize laureates have established an entirely new principle for cancer therapy."

The prize recognizes Allison's basic science discoveries on the biology of T cells, the adaptive immune system's soldiers, and his invention of immune checkpoint blockade to treat cancer. According to MD Anderson, Allison's crucial insight was to block a protein on T cells that acts as a brake on their activation, freeing the T cells to attack cancer. He developed an antibody to block the checkpoint protein CTLA-4 and demonstrated the success of the approach in experimental models.

Allison's work led to the development of the first immune checkpoint inhibitor drug which would become the first to extend the survival of patients with late-stage melanoma. Follow-up studies show 20 percent of those treated live for at least three years, with many living for 10 years and beyond, unprecedented results, according to the cancer center.

"Jim Allison's accomplishments on behalf of patients cannot be overstated," says MD Anderson president Peter WT Pisters, M.D., in a statement. "His research has led to life-saving treatments for people who otherwise would have little hope. The significance of immunotherapy as a form of cancer treatment will be felt for generations to come."

"I never dreamed my research would take the direction it has," Allison adds. "It's a great, emotional privilege to meet cancer patients who've been successfully treated with immune checkpoint blockade. They are living proof of the power of basic science, of following our urge to learn and to understand how things work."

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This story originally appeared on CultureMap.

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Houston-based Fervo Energy bumps up IPO target to $1.82 billion

IPO update

Houston-based geothermal power company Fervo Energy is now eyeing an IPO that would raise $1.75 billion to $1.82 billion, up from the previous target of $1.33 billion.

In paperwork filed Monday, May 11 with the U.S. Securities and Exchange Commission, Fervo says it plans to sell 70 million shares of Class A common stock at $25 to $26 per share.

In addition, Fervo expects to grant underwriters 30-day options to buy up to 8.33 million additional shares of Class A common stock. This could raise nearly $200 million.

When it announced the IPO on May 4, Fervo aimed to sell 55.56 million shares at $21 to $24 per share, which would have raised $1.17 billion to $1.33 billion. The initial valuation target was $6.5 billion.

A date for the IPO hasn’t been scheduled. Fervo’s stock will be listed on Nasdaq under the ticker symbol FRVO.

Fervo, founded in 2017, has attracted about $1.5 billion in funding from investors such as Bill Gates-founded Breakthrough Energy Ventures, Google, Mitsubishi Heavy Industries, Devon Energy (which is moving its headquarters to Houston), Tesla co-founder JB Straubel, CalSTRS, Liberty Mutual Investments, AllianceBernstein, JPMorgan, Bank of America and Sumitomo Mitsui Trust Bank.

Fervo’s marquee project is Cape Station in Beaver County, Utah, the world’s largest EGS (enhanced geothermal system) project. The first phase will deliver 100 megawatts of baseload clean power, with the second phase adding another 400 megawatts. The site can accommodate 2 gigawatts of geothermal energy. Fervo holds more than 595,000 leased acres for potential expansion.

Cape Station has secured power purchase agreements for the entire 500-megawatt capacity. Customers include Houston-based Shell Energy North America and Southern California Edison.

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This article originally appeared on our sister site, EnergyCapitalHTX.com.

Texas university's new flight academy opens at Houston Spaceport

cleared for takeoff

The vehicles may not have “student driver” stickers on them, but Texas Southern University has moved a dozen planes into its new training facility at the Houston Spaceport, opening the way for student flyers to use the facility.

TSU previously reached a deal with Houston Airports and the City of Houston in 2023 to house its prospective Flight Academy at Ellington Field. At the time, TSU had a small fleet of nine planes for student use, but a $5.5 million investment from the city greatly expanded the space available.

The Flight Academy includes a 20,000-square-foot hangar that serves as a TSU satellite campus. The school now has a fleet of 12 Cirrus SR20 aircraft that were acquired last year through state and alumni funding. An additional 4,500 square feet is used as classroom and office space. An 8,000-gallon fuel tank will support flight training operations.

TSU first launched its Aviation Science Management program in 1986 and added a professional pilot program in 2016. The school is now part of the United Airlines pipeline program and has also forged relationships with Delta and Southwest.

“I want to commend Texas Southern University and Houston Airports for their leadership and partnership in advancing aviation education right here in our city,” Houston City Councilwoman Dr. Carolyn Evans-Shabazz in a press release.

“It connects our students to high-paying, high-demand careers in aviation and aerospace. This is how we grow a city in the right way—by investing in workforce development, aligning education with industry and making sure our residents are prepared to lead in the industries of tomorrow. Houston is already a global leader in aerospace and projects like this strengthen that position even further, especially here at Ellington, where innovation and opportunity continue to take flight.”

The City of Houston signed an agreement to continue funding the academy for five years.

Amazon launches ultrafast, 30-minute delivery service across Houston

Amazon Now

More than 20 years after it redefined fast shipping, Amazon is preparing to raise the bar on consumer expectations again by offering to fulfill customers' most urgent product needs in Houston and other parts of the world in a half-hour or less for an extra fee.

The company, which revolutionized online shopping in 2005 with two-day deliveries for Prime members, is rapidly opening small order-processing hubs in dozens of U.S. and foreign cities to cater to shoppers who can't or don't want to wait for cough medicine to relieve flu symptoms or tomatoes for tonight's dinner salad.

The ultrafast service, called Amazon Now, first launched in India last June. Amazon says 30-minute deliveries now are also available in urban areas of the United States, Brazil, Mexico, Japan, the United Arab Emirates, the United Kingdom.

The mini-warehouses devoted to Amazon Now are about the size of a CVS drugstore. They stock about 3,500 products for expedited delivery, including beer, diapers, pet food, meat, nonprescription medications, playing cards and cellphone charging cables.

“We know that customers love speed and always have,” Beryl Tomay, Amazon’s head of transportation, told The Associated Press on Monday. “What we see customers doing, when we offer faster speeds, are they purchase more from Amazon. And Amazon becomes more top of mind for that or other types of items as well.”

In the U.S., the company first tested Amazon Now in Seattle, the home of its headquarters, and in Philadelphia. Most residents of the Dallas-Fort Worth area and Atlanta now have access as well. The service is also live in Dallas-Fort Worth, Denver, Minneapolis, Phoenix, Oklahoma City, Orlando, and dozens of other cities, Amazon said, with New York City and others expected by year-end.

The service charges for Amazon Now start at $3.99 for Prime members, who pay an annual fee of $139, and $13.99 for non-members. A $1.99 small basket fee applies to orders under $15, Amazon said.

The company's bet on a need for speed also comes as some consumers are rebelling against rushed deliveries as they weigh the potential impact on the environment and the workers tasked with preparing orders at a rapid rate.

Amazon’s approach
A relentless focus on speed helped Amazon build a logistics and e-commerce empire. After it made two days the new delivery time normal, Amazon moved into one-day and same-day deliveries for its Prime members. This spring, the company began making 90,000 products available in one hour or three hours at an extra cost.

The scaled down and sped up microhubs that are designed to handle 30-minute orders represent another step in Amazon's pursuit.

Only a handful of people prepare orders from aisles of shelves in the 5,000- to 10,000-square-foot facilities, unlike the sprawling fulfillment centers storing millions of items where Amazon employs a mix of human workers and robotics to pick and pack orders.

Amazon tailors the product inventory to each location and uses artificial intelligence and other technology to analyze what customers buy, as well as when and how often. The most popular U.S. purchases so far include soap, toothpaste, mouthwash, toilet plungers, bananas, limes and wireless earbuds, Amazon said.

The competition
Amazon’s attempt to up the instant gratification ante provides direct competition to on-demand food delivery platforms like Instacart, Uber Eats, DoorDash and Grubhub, which don't have the scale of the e-commerce titan, according to independent retail analyst Bruce Winder.

“What Amazon brings is their prowess in supply chain,” Winder said.

These smaller companies said they don't see Amazon as a threat, though, citing the hundreds of thousands of items they are able to deliver to users' doorsteps by partnering with various merchants and restaurants.

“DoorDash has a mission to empower grocers and retailers and augment their existing footprint, not to replace them,” DoorDash spokesperson Ali Musa said in an emailed statement. “We win only when they win, which is how we can offer over half a million grocery and retail items in under an hour across the country.”

Amazon also is in a race with Walmart to become the retailer that reliably gets orders to online shoppers in under an hour.

For an additional $10 on top of standard delivery charges, shoppers can place Walmart Express Delivery orders from among more than 100,000 products that are guaranteed to arrive in an hour. Many customers, however, are receiving the items under 30 minutes, Walmart CEO John Furner told analysts in February.

Domino's cautionary tale
Companies have promised deliveries in 30 minutes or less before, but the landscape also is littered with failed attempts to break the speed barrier.

The COVID-19 pandemic produced a flurry of companies that promised 10- to 15-minute grocery deliveries from microwarehouses in dense neighborhoods, according to Sucharita Kodali, an analyst at market research firm Forrester Research.

But soaring operating costs, low customer loyalty and the drying up of investor money ultimately caused most to fail before the pandemic was over, analysts said.

Domino’s in 1984 pushed a guarantee that customers would receive their pizzas for free if they weren't delivered in under a half-hour. The company amended the “30 minutes or it’s free” policy after two years, providing only a $3 discount for late deliveries.

The promotion helped Domino’s win market share, but it ended up tarnishing the company's reputation. It dropped the guarantee in December 1993 after a string of crashes and lawsuits involving drivers racing to meet the deadline.

Brad Jashinsky, a retail analyst at information technology research and consulting firm Gartner, said he thinks Amazon should take the pizza chain's experience as a cautionary tale.

“You get in trouble when you start overpromising something like that,” he said.

Amazon won't be making any time guarantees and instead plans to keep customers who chose the 30-minute delivery option updated on the progress of their orders, Tomay said.

“There's no rushing either in our building workers or the gig workers,” she said.

Taking it slow
Kodali thinks Amazon will need a lot of people placing orders around the same time from the same or adjacent apartment buildings for the 30-minute service to be cost-effective.

Consumers may appreciate rapid receipt of products like toilet paper and batteries, but retailers and logistics experts said they also see some online shoppers, especially members of Generation Z, choosing no-rush shipping for products they don't need in a hurry.

Amazon for several years has invited customers to skip one- or two-day delivery and to receive their orders on the same day in as few parcels as possible. Consolidating orders into fewer packages by electing to have them delivered at the same time cuts down on boxes, shipping envelopes and fuel use, analysts said.

“The millennials who came to age in an era that was on fast delivery came to expect it de facto, whereas ... Gen Z is more accepting of a slower speed than previous generations before them,” said Darby Meegan, a general manager at Flexport, a supply chain and logistics company that fulfills orders for thousands of online merchants.

Still, Amazon executives have cited positive early results for Amazon Now in India, where they said Prime members tripled their requests for 30-minute deliveries once they started using the service.

Amazon Now also is attracting more repeat American customers, Tomay said.

“It’s in early days and time will tell,” she said. “I think that it will be interesting to see how it evolves.”