Tag: Cancer Research

Southern Research breaks ground on new biotech center and campus renovations

Birmingham, Ala. – Southern Research today broke ground on a flagship biotech center that will anchor the development of 200,000 square feet of new or renovated wet lab space for life sciences. The new facility, located on the corner of Richard Arrington Jr., Blvd., and Ninth Avenue South, will double the organization’s lab space for researching infectious diseases and greatly expand its work to develop new treatments for cancer and other serious illnesses.

The new center is expected to create 150 new jobs at Southern Research and to double the institution’s annual economic impact to $300 million a year.

“This project represents a major investment in the city of Birmingham and in the great work being done by our Southern Research team,” said Josh Carpenter, Ph.D., president and CEO of Southern Research. “It builds on our strengths and puts us in a position for dynamic growth in the future.”

The Alabama Legislature included $45 million for the Southern Research building in the state budget for 2023, marking the state government’s first-ever investment in the 80-year-old campus.

“This represented an opportunity to create high-paying jobs in Birmingham and to support one of the state’s most important industries,” Gov. Kay Ivey said. “Scientific and technical innovation is a major driver of Alabama’s economic growth, and Southern Research has long been a key player in making it happen.”

Construction alone will create more than 1,100 project-related jobs and generate more than $190 million in economic activity, Carpenter said.

In addition to expanding space for research on infectious diseases like COVID-19, the new facility will allow Southern Research to ramp up its efforts to target common diseases that have a profound impact on the well-being of Alabamians and communities.

In addition to this new facility, Southern Research plans to renovate much of its campus and build new space to advance genomic diagnostics work over the next few years.

The city of Birmingham and Jefferson County have each been asked to provide funding alongside Southern Research and the State of Alabama to help accelerate this capital investment. While the contributions have not been approved at the City or the County, officials on both sides of Linn Park expressed support for the expansion.

“This is a transformational moment for Southern Research and for Birmingham,” said Birmingham Mayor Randall L. Woodfin. “As someone who benefited from a COVID-19 treatment developed with Southern Research’s experts, I am especially grateful to the scientists who work here and I’m proud to help them take their work to the next level.”

As Economic Development Committee Chair of the Jefferson County Commission, Steve Ammons called the Southern Research project yet another example of local leaders working across partisan and jurisdictional lines to benefit the entire Birmingham metro area.

“When we work together, we can do big things,” Commissioner Ammons said. “This expansion at Southern Research is an important project that will create economic ripples across this county and state.”

Ray Watts, MD, president of the University of Alabama at Birmingham and chair of the Southern Research board of directors, said the new facility will help fulfill his vision of creating a world-class biotech corridor that stretches from the UAB campus to Southern Research and Ascension St. Vincent’s Birmingham.

“Between UAB and Southern Research, we are working to ensure that Birmingham and Alabama become the biotech commercialization center of the Southeast,” Watts said. “This new facility will help us incubate new biotech entrepreneurs and attract top talent to this area. Southern Research and its vision for this center are intricately tied to the future success of Birmingham.”

Alongside the new construction, Southern Research has contracted Brasfield & Gorrie to help renovate more than 40,000 square feet of its existing campus facilities in Birmingham’s Southside. Investments include building out more vivarium space and launching a new clinical diagnostics lab.

Brendan Price: My journey through cancer led me to Southern Research, hope

A narrative by Brendan Price

For almost 25 years now, I’ve been in an unrelenting dance with cancer. It took my Mom. It claimed my wife. It came after me and pushed me to the brink. To get by, I needed a lot of support, from friends and family. To this day, I am amazed by the help I received. Believe me, I have seen lots of people sitting on waiting room couches all alone.

Of course, I wouldn’t be here today if it weren’t for great doctors and brilliant scientists working in places like Southern Research to discover treatments that give patients an increased chance for survival.

And I never lost hope. Hope, I discovered, is huge. It’s the golden side of a bad situation when you flip it over, like seeing the world while doing a handstand. I do a lot of those, about 10 a day. It gives me a different way of looking at things.

Southern Research
Brendan Price, a former gymnast, likes to do handstands because they help him view the world with a new perspective.

When cancer first arrived at my door, my life was rocking. I had returned to Texas, where I was coaching Elite level athletes alongside three-time Olympic Coach, Kevin Mazeika. Gymnastics was everything to me. I’d had a great gymnastics career at Southern Illinois University. I was even in the Guinness Book of World Records for the one-mile handstand relay.

Now I was back in Houston. I was young. I had spirit. I was healthy — seemingly.

But 1995 turned out to be a rough year. Early that year, my mom died of breast cancer. She waited too long to get a lump checked out. Her lesson to us was if you have a lump, go get it checked out. We were still in shock about my mother’s death when, bam, my diagnosis came, right out of nowhere. I was 31 years old.

THE DIAGNOSIS

It started with a swollen lymph node in my groin. It wouldn’t go away. When I went to the doctor, I was told it could be a number of things. Infected lymph gland. Cat scratch fever. So, I dismissed it at first. I didn’t feel sick. I wasn’t losing weight. I was working. Everything was good, but I had this lump.

Then the doctor called and said I should come in. It’s serious, she said. I ended up having a conversation sitting across from my doctor that no one ever wants to have. The diagnosis was Stage IV non-Hodgkin large cell B lymphoma. It was considered incurable. That scares a lot of people. And it scared me.

The treatment started immediately. I was given a cocktail of drugs. One of them was fludarabine, which was discovered at Southern Research, though I didn’t know that at the time. Chemo was difficult, no doubt about it. What fludarabine and that cocktail did for me, though, was to get me into remission.

Fludarabine helped me. It has helped a lot of people.

I was super happy about being in remission. My oncologist told me it wouldn’t last, that the cancer would come back. But I got five years of health, five years of a cancer-free life. It allowed me to meet my future wife, Jana, and marry her. I am forever grateful for that.

One day, a friend called about a job possibility in a new production at Disney World called “Festival of the Lion King.” They needed acrobats, so I started to get back into shape. I tried to do chin-ups. I probably ran all of 20 yards that first day. I got stronger and went to Orlando and auditioned with a bunch of young, healthy, ripped guys with full heads of hair. Despite feeling too old and too sick, Disney offered me the job.

Five years and one week after remission came the relapse.

It was my annual checkup in 2002. I felt tired, but I had been working really hard at Disney. It was a surprise, even though that’s the dynamic of the disease. The treatment started, and it was looking grim. An operation removed one third of my liver. The chemo wasn’t working. It was not looking good. I had a bone marrow transplant, and the recovery was slow. I was super sick.

Then, one day, I got a call from Jana. A checkup showed breast cancer. My mom, then me, now her. It was unbelievable. She went from being an amazing caregiver to a patient. We were both sick at the same time. One day, I might be her primary caregiver, the next day she might be mine. It was flip-flopping.

I got better. I’ve been in remission since 2003. When Jana died, she was 53, same age as my mother.

CRITICAL RESEARCH

Southern Research fludarabine
Diagnosed with lymphoma in 1995, Brendan Price’s treatment included fludarabine, a drug discovered at Southern Research.

After that, I moved to Asheville, North Carolina, a place we had loved. Later, I got a call from friends in Birmingham, and I have been here for three and a half years. Last fall, a friend invited me to her house to learn about Southern Research’s fundraiser, The Change Campaign. I was glad I went.

I heard about the seven cancer drugs that have been discovered at Southern Research. I knew all about fludarabine. I was lucky to speak to Dr. Rebecca Boohaker about my experience and how fludarabine had helped me. I even spent a morning with her and got a back-stage tour of what is going on at Southern Research.

I’m encouraged by the work taking place under one roof at Southern Research. There’s not only cancer research, but also neuroscience, green chemistry, and more. The possibilities are unlimited. I’m not sure a lot of people in Birmingham really know what they have here in Southern Research.

To some extent, cancer treatment has been and continues to be slash and burn. It’s about killing cancer cells, but there is collateral damage. The future of treatment is immunotherapy, and that is one of the things that is going on at Southern Research. I think people should get behind that, and donating to their cancer research program is one way to do that.

Today, the description of my status is cancer-free. My oncologists at UAB and I have talked about a “cure.” I don’t use that word for myself. It’s not that I am being negative. It’s that today, in this moment, I am alive, and I am healthy. Tomorrow, I might or might not be.

Through all this, I’ve learned that there can be a golden side to every bad situation when you flip it over. I’m reminded of that every time I do a handstand – inverted, looking at things with an entirely new perspective.

Read a story about how fludarabine helped young Liliana Thompson.

Researching radiosensitizers, a new class of drugs that would make tumors more vulnerable to radiation therapy

Two out of three cancer patients are treated with radiation, but the therapy often fails to wipe out the tumor or slow its growth. Southern Research is working to develop a new class of drugs that will help the radiation deliver a more powerful punch to the disease.

Dr. Bo Xu, M.D., Ph.D., Distinguished Fellow and Chair of Southern Research’s Oncology Department, said a radiosensitizer, as this kind of drug is known, would greatly benefit cancer patients by improving the success rate of radiation by reducing resistance to the treatment.

“Our project focuses on making those tumor cells more vulnerable to radiation by targeting a critical survival mechanism that allows them to recover from the effects of radiation,” Xu said.

It’s a challenging project, in the works for almost a decade. It got started when Southern Research scientists began looking at fundamental biology concepts to identify a pathway that could play a role in the ability of cancer cells to survive radiation.

Southern Research Bo Xu radiosensitizer
Southern Research’s Dr. Bo Xu is working to develop a radiosensitizer, a drug that would make tumors more vulnerable to radiation therapy.

They discovered that disrupting the tumor’s self-protection mechanism – in this case, an interaction between two specific proteins – makes the cancer more sensitive to radiation treatment, Xu said.

“The whole idea is to use this strategy to find a new drug that can be used by patients who receive radiation. This drug wouldn’t have toxicity because if it got into the cell it wouldn’t mess up the major functions of the protein network,” he said.

“It would only work when radiation is delivered, and that radiation would be more effective. It’s like a catalyst.”

Using funding from the Alabama Drug Discovery Alliance (ADDA), a partnership with the University of Alabama at Birmingham, Southern Research scientists recently scanned thousands of compounds to identify potential drug candidates. The focus now is to validate the results of those scans and to identify lead compounds for more testing.

“Our hope is that in three years, we can identify a novel class of radiosensitizers that can help the approximately two-thirds of cancer patients who will eventually receive radiotherapy,” Xu said.

CRITICAL INTERFERENCE

While some forms of cancer, such as lymphoma, are sensitive to radiation therapy, many others are not. Solid tumors with a low supply of oxygen, called hypoxic tumors, are tough to treat with radiation. So are cancer cells with a high DNA-repair capability.

To develop a radiosensitizer, Xu is taking aim at a protein that binds to DNA and recognizes the damage being done by radiation. The protein then joins forces with an enzyme to initiate a molecular repair job.

“If that recruitment is successful, then the DNA damage will be repaired, and the cancer cell will survive,” Xu said. “What we’re trying to do is to block this protein from finding the other one, so that the repair process will be diminished or affected. That way, the tumor cells will die.”

To prevent the DNA repair job from getting started, Xu is investigating a small peptide mimic, a small sequence of amino acids that is similar to a human protein but just a fraction of its size. These strands get to the site to block the interaction of the two natural, full-size proteins.

“This interference makes the cancer cell more vulnerable to radiation treatment,” he said.

Radiosensitizers are in demand, but they have proved difficult to develop. While the concept has been around for half a century, very few radiosensitizers have actually become available, according to Xu.

“While there are compounds that work synergistically with radiation, there are few drugs that were developed as a pure radiosensitizer,” he said.

In addition to the ADDA, the National Institutes of Health and the Department of Defense prostate cancer program have provided Southern Research with funding for this research over the years.

Helping clients with Immuno-Oncology research

Since Southern Research received its first contributions for cancer research in 1946, our scientists have been working independently and with U.S. government and commercial clients to understand and work toward cures for various cancers. During the organization’s 71-year history fighting this devastating disease, Southern Research has endeavored to stay on the front of this challenge. This commitment has led to the development of the first quantitative tumor models, the log-kill model, combination chemotherapy, and the discovery of seven approved chemotherapeutic drugs. Our Drug Development team has built a well-established reputation as a pioneer in anticancer drug development, having evaluated half of all FDA-approved anticancer drugs currently on the market. And we continue to evaluate hundreds more compounds annually to establish the in vitro biochemical effects and in vivo efficacy of potential new anticancer drugs.

The world’s “newest” tool helping to eliminate cancer is the human immune system. Southern Research is committed to helping clients working in the Immuno-Oncology realm the same way we have helped the cancer research community for the past seven decades. The first of our Immunology-Oncology models was presented at the 2016 Immuno-Oncology Summit in Boston. Since then, our efforts have continued. If you plan to attend the upcoming American Association for Cancer Research in Washington, D.C., our drug development scientists will be waiting to talk with you at the Southern Research booth, #2423, about our anticancer efficacy services.

 

Robert R. Meyer Foundation gift boosts Drug Discovery efforts

Birmingham’s Robert R. Meyer Foundation is supporting Southern Research’s Drug Discovery program with a $500,000 gift that aims to accelerate efforts to find new treatments for unmet medical conditions and rare and neglected diseases.

The contribution renews close ties between the Birmingham-based non-profit research organization and a charitable trust that became an important backer of its scientific work more than 60 years ago.

Southern Research has earned a solid reputation in drug discovery, with seven FDA-approved anticancer drugs, a number that ranks it among the most prolific in the field. In addition, Southern Research’s labs have screened many other potential medicines, and its researchers have developed a robust pipeline of promising therapeutics.

Southern Research Meyer Foundation
John Meyer, front row, second from right, stands for a photo at the dedication of Kettering-Meyer Lab II in 1958. His wife is next to him, and daughter Nancy behind him.

“The Robert R. Meyer Foundation’s longstanding support of Southern Research has been fruitful, contributing to many discoveries made by the organization’s scientists that have improved the lives of people battling cancer and other serious diseases,” said Beverly Baker, an Advisory Committee member for the foundation.

“The foundation’s leadership is confident that this gift will facilitate additional insights that lead the way to new treatments,” Baker added.

EARLY SUPPORT

The Meyer Foundation has supported Southern Research since 1953, when it provided $100,000 to match funding from the Charles F. Kettering Foundation for the construction of the Kettering-Meyer Laboratory. The Meyer Foundation made another significant contribution in 1957 to facilitate construction of a second Kettering-Meyer Lab.

In addition, the foundation has supported Southern Research’s cancer programs with other donations over the years.

“Significant gifts from the Robert R. Meyer Foundation in the 1950s enabled Southern Research to make important advances in drug discovery and have contributed to the impact our research and drugs have made on patients around the world,” said Art Tipton, Ph.D., president and CEO of Southern Research.

“The foundation’s latest gift will allow us to continue to explore important scientific breakthroughs that are high-risk, high-reward endeavors, rarely funded through government grants,” Tipton added. “This is the kind of research that results in the discovery of new drugs.”

Southern Research’s Drug Discovery division focuses on identifying novel treatments for serious conditions such as cancer, Parkinson’s disease, Alzheimer’s disease, diabetes, and viral and bacterial infections.

The division works as a partner of the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of Drug Abuse, among others. It also collaborates with the Cystic Fibrosis Foundation, the Muscular Dystrophy Foundation, and other non-profit organizations and research institutions.

“Southern Research has the unparalleled capacity to investigate a wide range of potential treatments for complicated conditions,” said Mark J. Suto, Ph.D., vice president of the Drug Discovery division.

“Our innovative research programs and unique technological capabilities position the scientists at Southern Research to investigate possibilities and achieve meaningful outcomes.”

IMPORTANT CONTRIBUTIONS

The Robert R. Meyer Foundation was formed in 1942, just one year after the founding of Southern Research. Over the years, it has contributed more than $65 million to hundreds of charitable organizations.

Robert Meyer was a prosperous hotel operator with properties in Birmingham; Baltimore; Jacksonville, Florida; Nashville and Knoxville, Tennessee; and Raleigh, North Carolina. He served on the boards of the Waldorf Astoria and Governor Clinton hotels in New York City, as well as local enterprises such as DeBardeleben Coal and Woodward Iron.

He also served on Southern Research’s board of directors in 1946, one year before his death. His son, John Meyer, became a member of the board the next year, serving until 1970.

John Meyer was optimistic that cancer research would unravel the mysteries of the deadly disease and yield new treatments. At the dedication ceremony for the Kettering-Meyer lab on Dec. 17, 1953, John Meyer introduced his oldest daughter, Jane, to those attending the event.

“It seems particularly appropriate that youngsters of Janie’s age group should play a part here since their generation undoubtedly will be among the largest beneficiaries of current cancer research,” John Meyer said. “It is not only possible, but altogether probable, that by the time this young lady reaches maturity, the battle with cancer will have been won.”

While the struggle has not yet been won, the Meyer Foundation’s latest gift will help Southern Research continue the fight through the search for new medicines.

National Cancer Institute awards major contract to Southern Research

Southern Research has been awarded a new, five-year Indefinite-Delivery Indefinite-Quantity (IDIQ) contract from the National Cancer Institute to investigate the pharmacokinetic properties of antitumor and other therapeutic agents of interest to the Division of Cancer Treatment and Diagnosis (DCTD) under NCI contract HHSN261201600021I.

Southern Research NCI contract
Bernard Ntsikoussalabongui and Katie Isbell of the Drug Development division study results in a Southern Research lab.

RFP number N02CM67000-11 was issued under full and open competition, which resulted in five IDIQ awards. Task orders will be competed among the five IDIQ Contractors in the award pool and placed off of the IDIQ as requirements arise.

This IDIQ contract is one of three long-term contracts the Birmingham-based organization holds with the NCI to support its objective of developing compounds against cancer and other diseases.

“Southern Research has been working with the NCI for over 30 years with one goal in mind: helping advance the pipeline of potential drug candidates so the NCI can move forward with clinical trials,” said Sheila Grimes, D.V.M., Ph.D., D.A.C.V.P., pathology program leader and principal investigator on the project for Southern Research.

KEY ANALYSIS

Pharmacological testing is an integral part of the drug discovery and drug development processes. In order for clinical trials to commence with a candidate compound, researchers must first answer questions pertaining to how the drug interacts with, and exists within, the human body.

To accomplish this goal, Southern Research will employ a number of tests to explore in vivo tumor models and analyze the bioanalytic makeup of the compound. Under the scope of the contract, the organization is tasked with evaluating how the sample drug moves through a living system and analyzing the amount of time required for candidate compounds to break down within a system, or under a range of conditions.

“Southern Research has worked closely with the NCI for more than 30 years, and we are proud to continue those efforts in this program defining the pharmacokinetics of the next generation of anticancer medications,” said Art Tipton, Ph.D., president and CEO of Southern Research.

“The trinity of government, industry, and nonprofit research organizations like Southern Research is a necessary collaboration to enable most drugs to reach the market. We’re pleased to continue our role, and I commend our team for their ongoing extraordinary work in the field.”

Southern Research at 75: Discovering cancer drugs and extending lives

Southern Research scientists have been attacking cancer since the organization’s early days, developing successful approaches to chemotherapy, screening biological agents that kill cancer cells, and making other advances.

A key contribution to this fight involves the organization’s track record for discovering FDA-approved anticancer medicines.

“Of the 200 or so drugs currently used to treat cancer, seven were discovered at Southern Research,” Dr. Francis Collins, director of the National Institutes of Health, said in a video message to mark the Birmingham-based non-profit’s 75th anniversary in October.

Southern Research dacarbazine
Dacarbazine became Southern Research’s first FDA-approved cancer drug in 1975.

Collins noted that two of Southern Research’s cancer drugs are on the World Health Organization’s List of Essential Medicines, indicating their critical importance to oncology. They are fludarabine, a treatment for chronic lymphocytic leukemia (CLL), and dacarbazine, used against malignant melanoma and Hodgkin’s lymphoma.

“At Southern Research, we have developed seven anticancer drugs and made critical advances in basic research that have deepened our understanding of cancer,” said Art Tipton, Ph.D., the organization’s president and CEO.

“We will continue to use our deep science and development tools to work toward novel treatments for a disease that kills a half million Americans each year,” he added.

Southern Research’s first anticancer drug, dacarbazine, received FDA approval in 1975 and remained a front-line treatment against melanoma for many years. Its seventh FDA-approved drug, pralatrexate, entered the market in 2009 as a treatment for aggressive blood cancers.

EXTENDING LIVES

The road to FDA approval is long, as the timeline for pralatrexate demonstrates.

Research on drugs in this class began in the 1950s at California’s SRI International. A partnership between Southern Research, SRI and New York’s Memorial Sloan Kettering led to clinical trials on related compounds beginning in the 1980s.

SR 75th_Logo_Horz_RGBOnce pralatrexate was identified as viable clinical candidate, it was licensed to Allos Therapeutics for additional development in 2002. FDA approval for pralatrexate (brand name: Folotyn) as a treatment for peripheral T-cell lymphoma came in 2009 – six decades after the initial research began.

“We prepared and tested many compounds before finally identifying a substance that gave favorable results,” Southern Research organic chemist Robert Piper said at the time. “We are very glad our compound will help alleviate human suffering and extend lives.”

Piper’s role was to synthesize quantities of high-purity pralatexate used in preclinical investigations.

Piper was also involved in the discovery of amifostine, an FDA-approved medicine that protects patients from harmful effects associated with radiation treatment and chemotherapy.

THE ‘DREAM TEAM’

The foundation of Southern Research’s success in drug discovery was laid in the 1950s, when the organization assembled what former CEO Jack Secrist, Ph.D., has called the “Dream Team” in cancer research.

Under the overall direction of Howard Skipper, the leadership team was composed of John Montgomery, Frank Schabel and Lee Bennett, who headed the Organic Chemistry, Chemotherapy and Biochemistry departments at Southern Research, respectively.

“They worked together for many years, and together with their staff, were a very effective team,” Secrist said in an interview.

Southern Research cancer team
The Southern Research ‘Dream Team’, from left, Frank Schabel, Lee Bennett, Howard Skipper, and John Montgomery.

The Southern Research team established an efficient and effective approach to the development of potential new drugs, he said.

“New compounds were evaluated rapidly, and those with potential were subjected to more detailed evaluations as soon as possible, and compounds that had no activity or weak activity were set aside to make way for new compounds,” said Secrist, who once headed Southern Research’s Drug Discovery division.

This approach to drug discovery is still in use at Southern Research today, he added.

The contribution of Montgomery, a member of Southern Research’s cancer team for more than 40 years, was particularly significant. He was involved in the discovery of five FDA-approved anticancer drugs: lomustine, carmustine, dacarbazine, fludarabine, and clofarabine.

“This is what we all aspire to as drug discovery researchers, moving life-saving compounds from conception to clinic,” said Secrist, co-inventor of clofarabine with Montgomery.

Read a story about how clofarabine helped save the life of a teenage leukemia patient.

 

This is Part Nine of a series looking at the history of Southern Research.

NIH director thanks Southern Research for ‘treatments, cures and real hope’

In a message to mark Southern Research’s 75th anniversary, Dr. Francis S. Collins, director of the National Institutes of Health, praised the organization’s scientists for making significant advances against cancer and other diseases.

“Since 1941, Southern Research has made advances that have helped people all across this country – in fact, all around the globe,” Collins said in a video shared with the Birmingham-based non-profit.

In particular, the leader of NIH, the nation’s chief medical research agency, noted the achievements of Southern Research’s long-standing cancer research program. The organization’s scientists played key roles in developing effective chemotherapy methods and in the discovery and development of numerous FDA-approved oncology treatments.

“Of the 200 or so drugs currently used to treat cancer, seven were discovered at Southern Research,” Collins said. “In fact, two of them – fludarabine and clofarabine – are even on the World Health Organization’s list of essential medicines.”

In addition, Southern Research has provided vital research tools and models that allowed other scientists to advance the development of cancer therapeutics, he said.

TARGETING DISEASES

While efforts to discover new oncology drugs continues at Southern Research, Collins noted that its scientists are also working on potential therapeutics for Alzheimer’s, Parkinson’s, diabetes, Lou Gehrig’s disease, and tuberculosis, among others.

At the same time, Southern Research is helping researchers around the world test new disease-fighting strategies. “The area of HIV/AIDS research has been a real standout,” he said.

Collins singled out Southern Research’s work in the field of reproductive toxicology, which seeks to prevent birth defects, and on the Zika virus, which has suddenly emerged as a serious threat to public health around the world.

Collins also responded to a letter from Southern Research CEO and President Art Tipton, Ph.D., who thanked the NIH for providing the Birmingham non-profit with more than $500 million in funding over the past three decades.

“Mr. Tipton, I want to let you, along with all of Southern Research and its supporters, know that you are indeed welcome,” Collins said. “And on behalf of the NIH and the American taxpayer, I want to thank you, Southern Research, for a tremendous return on this investment – a return measured in treatments, cures and real hope for a better future for people all around the world.

National Cancer Institute extends toxicology contract with Southern Research

NCI extends long-term toxicology contract with Southern Research.
NCI extends long-term contract with Southern Research for preclinical toxicology screening of cancer drugs.

Southern Research has been awarded a five-year IDIQ contract with a potential value of $19 million from the National Cancer Institute (NCI) to study the preclinical toxicology of new drugs under development for the treatment of cancer — contract number HHSN261201600018I.

The contract is one of three ongoing contracts between Southern Research and the NCI, and has been in place continuously since 1979. This is the latest in a series of contract extensions for the organization.

The two additional ongoing contracts between Southern Research and the NCI are for research on the pharmacology of potential new cancer drugs, and for evaluation of drugs intended for the prevention of cancer.

“Our ultimate goal with this contract is to help the NCI develop an understanding of how different drug candidates interact with and affect living systems,” said Charles Hébert, Ph.D., senior program leader and principal investigator on the project for Southern Research. “The collection of this information is necessary so the FDA can determine whether a particular drug candidate is safe for clinical trial testing in humans.”

Toxicology testing is an integral part of the drug development process. In order to determine the safety of a new drug candidate, researchers must first conduct dose range-finding studies to establish the maximum tolerated dose, and to aid in the selection of dose levels for use in further testing.

Once the appropriate dose range has been established for the selected species, larger and more detailed definitive studies are conducted. Those definitive studies differs from dose range-finding studies in that they require deeper and more thorough analysis of the ways a particular drug may affect animals, and by extension, humans. Ultimately, the definitive studies provide key information that is used by the FDA to determine the recommended dose options for any drug candidate approved for clinical trial.

“Southern Research has been at the pioneering forefront of cancer research for more than 70 years, and we are particularly proud of our work with the National Cancer Institute,” said Art Tipton, Ph.D., president and CEO of Southern Research. “We have invested heavily to develop unique capabilities and institutional knowledge in this field, and work diligently to stay on the forefront of the field enabling us to improve people’s lives by finding cures to some very challenging diseases.”

Clofarabine co-inventor Jack Secrist talks about drug discovery

Drug discovery researchers like Jack Secrist are motivated by a strong desire to see their work save lives and make a profound difference.

Secrist, the former head of Drug Discovery at Southern Research, is co-inventor of clofarabine, a drug approved by the Federal Drug Administration in 2004 for acute lymphoblastic leukemia (ALL) in pediatric patients like Frances Grace Hirs.

Frances Grace was battling a third bout of ALL in 2013 when she was treated with clofarabine, which helped put her on the road to recovery. (Read a story about her treatment.)

clofarabine-poster“This is what we all aspire to as drug discovery researchers, moving life-saving compounds from conception to clinic,” Secrist said in 2005, shortly after clofarabine received FDA approval.

In a new interview, Secrist talks about how he and his Southern Research colleagues discovered clofarabine and how the drug moved along to the path to become the first treatment for childhood cancer approved by the FDA in more than a decade.

In this Q&A, Secrist also shares his views on how Southern Research, which has discovered seven FDA-approved drugs used in cancer treatment, has been able to consistently develop new therapies that address unmet medical needs.

Southern Research was visited recently by Frances Grace Hirs, who was treated with clofarabine after a second leukemia relapse. Her parents credit the drug with stabilizing her condition, making a bone marrow transplant possible. As a co-inventor of the drug, do you hear stories like this often?

Secrist: In my experience, at least as it pertains to chemists who are inventors of cancer drugs that end up being FDA approved, it is rare that you would meet someone who had benefited from the drug unless it happens to be a family member, friend, or acquaintance. The inventors are far removed from both the oncologists who select the drugs and the patients who take them.

Southern Research Secrist
Clofarbine co-inventor Jack Secrist

In this situation, I can relate two stories. I did meet a father and a daughter who had benefited from the drug in Birmingham, and they were focused on making sure that others who might benefit from the drug would be appropriately informed.

The other time that I saw patients who benefited from the drug was at the FDA hearing where the drug was approved. A father brought his son to the hearing and he took advantage of the public forum to relate the story of his son and how this drug has certainly saved his life. He was holding the boy, who was perhaps five or six, in his arms as he spoke. It was a moving scene.

How did the work that led to clofarabine get started?

Secrist: This question is somewhat more technical, but I will provide some information about how we moved toward the drug that became clofarabine. First, we were working in the nucleoside area, looking for drugs that would affect DNA function in cancer cells, which was at the time the best way to develop a new cancer drug. We chose to work on nucleosides since they are the building blocks of DNA, and we felt that finding something that would be recognized by the cancer cells, and perhaps have selectivity, was more likely in this area.

At the time, around 1983, we had funding from National Institutes of Health (NIH) in the form of what is called a program project grant to search for new drugs in this area, and to evaluate them in biological systems. There were two potential drugs that looked promising at the time that were nucleosides, and we had the detailed biological data to be aware of structural concerns with both drugs.

Southern Research Secrist
Jack Secrist, at the whiteboard, speaks to members of the Southern Research cancer team. John Montgomery is seated at the head of the table.

John Montgomery (an organic chemist and key member of the cancer research team) and I then formulated a plan to make a series of new compounds that would be similar enough that they might have activity, but would have structural changes that would overcome the concerns we saw with these two potential drugs. We made this series of compounds, and the end result was clofarabine.

By the way, both of the other compounds also became FDA approved: one of them is fludarabine and the other is cladribine. Interestingly, the three compounds, though very similar in structure, are used for different forms of leukemia.

Can you recount any significant developments or insights that occurred during your work on this project?

Secrist: The first insight that we developed, which really was just a confirmation of what we already felt, was that very small changes in the structure of a molecule can result in very large changes in biological and clinical activity. The utility of clofarabine, fludarabine and cladribine is a clear demonstration of that fact, and it can be seen in other areas, as well.

Another insight that was strengthened was that the more robust the biological (anticancer) data is on a compound, the more likely it is to become FDA approved. Compounds with some activity and selectivity, but not really strong data, most likely will not make it through to approval. Clofarabine had very strong data supporting its move into clinical trials.

It is also true, by the way, that there is not a connection between what human tumors a potential drug can cure in model systems and what tumors it may cure in humans. It would be wonderful if that was the case, but at least with the current models no such correlation exists. Again, we get back to the fact that robust activity and selectivity data across a wide range of tumor types is the best indicator.

When clofarabine received FDA approval in 2004, it was the first new pediatric leukemia to hit the market in more than a decade. How would you assess its significance?

Secrist: Thinking back to the clinical development of the drug, which started at M. D. Anderson Cancer Center in Texas, there was a critical chance happening. A family had a child who had gone through the available drugs for his leukemia, and he was not responding. They asked to be able to try clofarabine, which was not yet available for trials, and their request was granted. The child responded immediately, and the family was truly grateful.

That chance happening suggested the best path to approval, that is, through a focus on childhood leukemia, though there were of course adult trials as well. The drug clearly helped children, and the FDA was very interested in finding a new drug for childhood cancers, and they were very helpful and supportive.

When the ODAC (Oncology Drug Advisory Committee), a group of outside clinicians, voted for approval, the FDA was really pleased to have the first new drug to treat childhood cancers in more than a decade.

Southern Research has discovered seven drugs used in cancer treatment. What made the organization such a hotbed for the discovery of anticancer drugs?

Secrist: In considering why Southern Research was so successful in developing new cancer drugs, I believe that there are a number of reasons. First, we had extremely talented scientists who were dedicated to the development of new drugs that would be useful in the treatment of cancer. The Dream Team in that regard comprised Howard Skipper, John Montgomery, Frank Schabel, and Lee Bennett. They worked together for many years, and together with their staff, were a very effective team.

Southern Research cancer team
The Southern Research ‘Dream Team:’ from left, Frank Schabel, Lee Bennett, Howard Skipper, and John Montgomery.

Second, that team developed an efficient and effective approach to the development of potential new drugs. New compounds were evaluated rapidly, and those with potential were subjected to more detailed evaluations as soon as possible, and compounds that had no activity or weak activity were set aside to make way for new compounds. This iterative approach to drug discovery is still in use today, though the biological systems have evolved over the years.

Finally, in the early years the Dream Team had not only their own ideas on the type of compounds to pursue in the search for new cancer drugs, but also the input of the cancer research team at the NIH. Thus, Southern Research scientists had access to the latest information available to NIH, including areas of activity, clinical results, and evaluation model advances.

In the early years Institute scientists would go up to NIH to present results, and would of course hear presentations about the results of others. In later years we used scientific meetings and personal contacts to gain that information. The result was an ability on our part to look in more fertile fields for new cancer drugs.