Blast Injuries

U.S. veterans of the wars in Afghanistan and Iraq who suffered mild traumatic brain injury from exposure to explosive blasts were found to have changes in cerebrospinal fluid proteins that are typically seen in people who develop Alzheimer's disease, according to researchers. U.S. veterans of the wars in Afghanistan and Iraq who suffered mild traumatic brain injury from exposure to explosive blasts were found to have changes in cerebrospinal fluid proteins that are typically seen in people who develop Alzheimer's disease, according to researchers at the University of Washington School of Medicine and VA Puget Sound Health Care System. "While our research does not prove that veterans who experienced these injuries will develop Alzheimer's disease, it raises the possibility that they may be on a pathway leading to dementia," said Dr. Ge Li, the paper's first author and an associate professor of psychiatry and behavioral sciences at UW Medicine. The study was published March 13 in the journal Neurology. Previous research has found that sustaining a moderate to severe TBI increases a person's risk of developing Alzheimer's disease. It is not known, however, whether a mild TBI (mTBI) similarly increases this risk. In the new study, the researchers analyzed protein levels in spinal fluid from 51 U.S. veterans of the wars in Afghanistan and Iraq. Each had suffered mTBIs from exposure to explosive blasts and had an average of 20 blast injuries. Those protein levels were compared with the protein levels of 85 veterans and civilians of similar age who had never sustained a TBI. In this study, the veterans were considered to have experienced a TBI if they had an alteration or loss of consciousness from the blast. The TBIs were considered mild if the loss of consciousness lasted 30 minutes or less and there was no sign of brain damage on standard clinical MRI or CT scan. Such an injury is considered equivalent to a concussion. The researchers examined protein levels in the veterans' cerebrospinal fluid, which flows around and through the brain and carries away waste materials. Two of the proteins measured compose the chief components of amyloid plaques, which aggregate in the brains of people with Alzheimer's. These proteins are called alpha-beta amyloid 40 and 42 (Aβ40, Aβ42). The other proteins are versions of the tau protein. Normally, tau proteins are part of cells' cytoskeletons, which give cells their shape. But with Alzheimer's, these structures are changed, creating tangles within brain cells and killing them. This is the other hallmark of Alzheimer's. With Alzheimer's disease, the levels of alpha-beta amyloid proteins in spinal fluid typically decrease. Researchers hypothesize that the proteins, instead of being flushed out into the spinal fluid and carried away as they normally would be, are deposited in amyloid plaques and remain in the brain. As the disease progresses, tau levels, in contrast, tend to be higher than normal, as the proteins are released from dying brain cells. In the study, mTBI veterans in their late 40s and 50s had lower levels of beta-amyloid proteins, compared with the veterans and civilians who had not had such injuries. Tau protein levels also were abnormal in the older mTBI veterans. Normally, tau levels rise as we age. But among the older middle-aged mTBI veterans, levels tended to remain the same, a finding that the normal brain clearance system may not be working as well in among the people with mTBI. Among older mTBI veterans, having lower beta-amyloid 42 levels was also associated with doing less well on cognitive tests assessing verbal memory and fluency. The decline in beta-amyloid proteins, in particular beta-amyloid 42, was concerning, said senior author Dr. Elaine Peskind, a UW research professor of psychiatry and director of the VA's Northwest Mental Illness Research, Education, and Clinical Center. "A decline in beta-amyloid 42 is the earliest detectable change due to Alzheimer's that can be found in a cognitively normal person," she said. "The change can appear as much as 20 years before symptoms. So a person can have the pathology of Alzheimer's going on in their brain but still not have any symptoms -- no problem with their memory or thinking functions -- for as long as 20 years." Peskind and her collaborators suspect the cause of the changes in the mTBI veterans' spinal fluid proteins is due to blast-related damage to a system in the brain, called the glymphatic system, that allows fluids to flow through the brain and carry away waste products. To find out, they have been funded by the National Institute of Neurological Diseases and Stroke to study the regulation and function of this system in veterans with these injuries.

– Positive top line results from the V005 Phase 2/3 trial of the Human Acellular Vessel™ (HAV™) in vascular trauma repair – – BLA for an indication in vascular trauma planned to be filed with the FDA during the current quarter – - Conference call and live webcast at 4:30 p.m. ET today - DURHAM, N.C., Nov. 09, 2023 (GLOBE NEWSWIRE) -- Humacyte, Inc. (Nasdaq: HUMA), a clinical-stage biotechnology platform company developing universally implantable, bioengineered human tissue at commercial scale, today announced financial results for the third quarter ended September 30, 2023 and highlighted recent corporate accomplishments advancing the investigational, universally implantable Human Acellular Vessel (HAV) closer to planned U.S. market launch. “The major milestones reached during the third quarter of 2023 set the stage for our planned Biologics License Application (BLA) filing of the HAV for the vascular trauma indication with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2023,” said Laura Niklason, M.D., Ph.D., Chief Executive Officer of Humacyte. “A key event supporting the planned BLA filing was our announcement of positive top line results from the V005 trial in vascular trauma repair. We are also proud that our humanitarian efforts in Ukraine, which will supplement the V005 results in our BLA filing, have resulted in successful outcomes including saving lives and limbs in a wartime setting. Finally, we are pleased that the potential of the HAV pipeline has also been observed in other clinical studies this quarter, including the presentation of Phase 2 results in severe peripheral arterial disease (PAD). In addition, we recently published preclinical results of our small caliber HAV in a juvenile heart disease model. The remainder of 2023 will be exciting, and we thank the medical professionals, patients, researchers and employees for their contribution to the advancement of the HAV.” Third Quarter 2023 Corporate Highlights Clinical and Regulatory Updates Positive Phase 2/3 Trauma Results – In September 2023, Humacyte announced positive top line results from its V005 Phase 2/3 trial of the HAV in vascular trauma repair. In this single-arm clinical trial, the HAV had higher rates of patency, and lower rates of amputation and infection, compared to historic synthetic graft benchmarks. A total of 69 patients were enrolled in the V005 trial, of which 51 had vascular injury of the extremities and comprised the primary evaluation group for the study. The 30-day patency (presence of blood flow) for the HAV in the clinical trial was 90.2% for the extremity patients compared to approximately 81% historically reported for synthetic grafts. The HAV demonstrated lower amputation rates, with a rate of 9.8% compared to over 20% historically reported for synthetic grafts. The HAV also demonstrated lower rates of infection, with a rate of 2.0% compared to over 8% historically reported for synthetic grafts.Planned BLA Filing this Quarter – Humacyte plans to file a BLA for the HAV for the treatment of vascular trauma with the FDA during the current quarter. Presentations and Publications Upcoming Presentations at a Major Vascular Surgery Symposium – Multiple presentations are expected to be made at the VEITH Symposium, a major vascular surgery meeting, in New York City on November 15-18, 2023. These include an expanded presentation of the results of the V005 vascular trauma trial, and the outcome of research which seeks to identify which dialysis patients experience the most difficulties with their dialysis access, and which patients may most benefit from an access that is durable and resists infection.Publication of Preclinical Results in Juvenile Heart Disease Study – In October 2023, a publication in the Journal of Thoracic and Cardiovascular Surgery described a preclinical study showing the potential for the investigational small-diameter HAV to treat tetralogy of Fallot, a heart condition that affects one in every 2,000 babies born each year. In the preclinical study, researchers from Nationwide Children's Hospital (Columbus, OH) and Humacyte implanted 3.5mm diameter HAVs into a juvenile large-animal model of pediatric heart disease. The 3.5mm HAVs remained patent for up to six months, and evidence of HAV repopulation by host cells was observed, similar to what has been observed in human patients. This study also demonstrates the extension of Humacyte’s manufacturing platform, adding production of the 3.5mm vessels in the same manufacturing platform used to produce Humacyte’s 6 mm HAVs that are in current clinical use.Presentation of Results from Phase 2 Study in PAD – In September 2023, results were presented from an FDA-regulated, investigator-sponsored clinical study conducted at the Mayo Clinic of the HAV in patients with chronic limb-threatening ischemia, the end stage of peripheral artery disease (PAD). In the presentation at the Midwestern Vascular Conference in Minneapolis, MN, researchers observed that in the clinical study the HAV was a safe, resilient, and effective conduit for arterial bypass and limb salvage. This is an important result since approximately 40% of patients requiring lower extremity bypass do not have saphenous vein available, which is the standard of care for treating this challenging disease state.Presentation of Success in Treating Wartime Injured in Ukraine – Results of the real-world use of the HAV under the humanitarian aid program to treat war-induced vascular trauma injuries in Ukraine were presented in August at the 2023 Military Health System Research Symposium (MHSRS) in Kissimmee, Florida. The 19 patients treated under the program suffered from a range of traumatic injuries, including gunshots, shrapnel, blast injuries and accidents. Clinicians reported that the rate of success in treating patients with the HAV was high, with an observed 30-day HAV patency of 95%, 30-day limb salvage of 100%, 30-day survival of 100%, and zero cases of infection of the HAV. Ukrainian clinicians concluded that the HAV has the potential to offer combat surgical teams an off-the-shelf and universally implantable therapy that is resistant to infection, potentially offering durable performance to military personnel and helping with limb salvage. Results from the Ukraine program will be included in Humacyte’s planned BLA filing with the FDA.Publication Supporting Infection Resistance of HAV – In July 2023, a preclinical study demonstrated a possible scientific basis for the low rates of infection that have been observed in clinical trials of the HAV. The report was published in the Journal of Vascular Surgery – Vascular Science. This work compared the infection resistance of the HAV to synthetic polytetrafluorethylene (ePTFE) grafts, which are made of plastic. The laboratory results suggest that the bioengineered human tissue of the HAV may have superior compatibility with the body's own white blood cells as compared to ePTFE. While human white blood cells die when they come in contact with ePTFE, the cells survive and function in contact with the HAV material, which may improve the ability of the HAV to fight dangerous infections once implanted in the body. The HAV is an investigational product and has not been approved for sale by the FDA or any other regulatory agency. Third Quarter 2023 Financial Highlights The Company reported cash and cash equivalents of $100.0 million as of September 30, 2023. In May 2023, Humacyte reported the completion of a funding arrangement of up to $160 million with Oberland Capital Management, $40 million of which has been received. Total net cash used was $49.4 million for the first nine months of 2023, compared to $53.8 million for the first nine months of 2022. Humacyte believes that its cash and cash equivalents and expected funding from the Oberland arrangement are adequate to finance operations past the currently anticipated timelines for FDA approval and commercialization of the HAV in the vascular trauma indication.There was no revenue for the third quarter of 2023 and nine months ended September 30, 2023. Revenue was $31 thousand for the third quarter of 2022 and $1.6 million for the nine months ended September 30, 2022. Revenue for 2022 was related to a grant supporting the development of the HAV.Research and development expenses were $18.6 million for the third quarter of 2023, compared to $17.3 million for the third quarter of 2022, and were $56.4 million for the nine months ended September 30, 2023, compared to $48.3 million for the nine months ended September 30, 2022. The current-period increases resulted primarily from increased personnel and external services expenses to support expanded research and development initiatives and our clinical trials, including preparation for the HAV vascular trauma trial completion and planned BLA filing for the vascular trauma indication, and expansion of clinical development of the HAV in AV access for hemodialysis.General and administrative expenses were $6.1 million for the third quarter of 2023, compared to $6.2 million for the third quarter of 2022, and were $17.5 million for the nine months ended September 30, 2023, compared to $17.1 million for the nine months ended September 30, 2022. The increase during the nine months ended September 30, 2023 compared to the prior-year period resulted primarily from increased personnel costs, primarily driven by preparation for the planned commercial launch of the HAV in the vascular trauma indication. The slight decrease during the third quarter of 2023 compared to 2022 resulted primarily from a decrease in external services and professional fees, partially offset by an increase in personnel expenses.Other net income (expense) was net expense of $1.4 million for the third quarter of 2023, compared to net expense of $1.8 million for the third quarter of 2022, and other net expense of $11.8 million for the nine months ended September 30, 2023, compared to other net income of $55.5 million for the nine months ended September 30, 2022. The decrease in other net expense for the third quarter of 2023 compared to 2022 resulted primarily from an increase in interest income due to rate increases. The increase in other net expense for the nine months ended September 30, 2023 compared to 2022, resulted primarily from the non-cash remeasurement of the contingent earnout liability associated with the August 2021 merger with Alpha Healthcare Acquisition Corp.Net loss was $26.0 million for the third quarter of 2023, compared to $25.3 million for the third quarter of 2022, and net loss was $85.7 million for the nine months ended September 30, 2023, compared to $8.2 million for the nine months ended September 30, 2022. The current-period increases in net loss resulted from the non-cash remeasurement of the contingent earnout liability, and increased operating expenses, described above. Conference Call and Webcast Details Title: Humacyte Third Quarter 2023 Financial Results and Corporate UpdateDate: Thursday, November 9, 2023Time: 4:30 p.m. ETConference Call Details: Toll-Free: 1-888-999-5318International: 1-848-280-6460Conference ID #: 13741924Call meTM Feature (avoid waiting for operator): Click HereWebcast: Webcast Link - Click Here A replay of the webcast will be available following the conclusion of the live broadcast and will be accessible on the investors section of the Company’s website for at least 30 days. About Humacyte Humacyte, Inc. (Nasdaq: HUMA) is developing a disruptive biotechnology platform to deliver universally implantable bioengineered human tissues, advanced tissue constructs, and organ systems designed to improve the lives of patients and transform the practice of medicine. The company develops and manufactures acellular tissues to treat a wide range of diseases, injuries, and chronic conditions. Humacyte’s initial opportunity, a portfolio of HAVs, is currently in late-stage clinical trials targeting multiple vascular applications, including vascular trauma repair, AV access for hemodialysis, and peripheral arterial disease. Preclinical development is also underway in coronary artery bypass grafts, pediatric heart surgery, treatment of type 1 diabetes, and multiple novel cell and tissue applications. Humacyte’s 6mm HAV for AV access in hemodialysis was the first product candidate to receive the FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation and has also received FDA Fast Track designation. Humacyte’s 6mm HAV for urgent arterial repair following extremity vascular trauma also has received an RMAT designation. The HAV received priority designation for the treatment of vascular trauma by the U.S. Secretary of Defense. For more information, visit www.Humacyte.com. Forward-Looking Statements This press release contains forward-looking statements that are based on beliefs and assumptions and on information currently available. In some cases, you can identify forward-looking statements by the following words: “may,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties, and other factors that may cause actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we caution you that these statements are based on a combination of facts and factors currently known by us and our projections of the future, about which we cannot be certain. Forward-looking statements in this press release include, but are not limited to, statements regarding the initiation, timing, progress, and results of our preclinical and clinical trials; the anticipated characteristics and performance of our HAVs; our ability to successfully complete, preclinical and clinical trials for our HAVs; the anticipated benefits of our HAVs relative to existing alternatives; the anticipated commercialization of our HAVs and our ability to manufacture at commercial scale; the implementation of our business model and strategic plans for our business; the timing or likelihood of regulatory filings and approvals, including the BLA for our V005 clinical trial; timing, scope, and rate of reimbursement for our HAVs; and our estimated available market opportunity. We cannot assure you that the forward-looking statements in this press release will prove to be accurate. These forward-looking statements are subject to a number of significant risks and uncertainties that could cause actual results to differ materially from expected results, including, among others, changes in applicable laws or regulations, the possibility that Humacyte may be adversely affected by other economic, business, and/or competitive factors, and other risks and uncertainties, including those described under the header “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2022 and in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, each filed by Humacyte with the SEC, and in future SEC filings. Most of these factors are outside of Humacyte’s control and are difficult to predict. Furthermore, if the forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. Except as required by law, we have no current intention of updating any of the forward-looking statements in this press release. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Humacyte Investor Contact:Joyce AllaireLifeSci Advisors LLC+1-617-435-6602jallaire@lifesciadvisors.cominvestors@humacyte.com Humacyte Media Contact:Rich LuchettePrecision Strategies+1-202-845-3924rich@precisionstrategies.commedia@humacyte.com Humacyte, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(unaudited)(in thousands except for share and per share amounts) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2023 2022 2023 2022 Grant revenue$— $31 $— $1,565 Operating expenses: Research and development 18,552 17,337 56,370 48,303 General and administrative 6,070 6,188 17,495 17,050 Total operating expenses 24,622 23,525 73,865 65,353 Loss from operations (24,622) (23,494) (73,865) (63,788) Other income (expense), net: Change in fair value of contingent earnout liability (1,144) (962) (11,708) 58,649 Other expense (net) (229) (825) (97) (3,106)Total other income (expense), net (1,373) (1,787) (11,805) 55,543 Net loss and comprehensive loss$(25,995) $(25,281) $(85,670) $(8,245) Net loss per share, basic and diluted$(0.25) $(0.25) $(0.83) $(0.08)Weighted-average shares outstanding, basic and diluted 103,444,246 103,031,980 103,357,087 103,014,009 Humacyte, Inc.Condensed Consolidated Balance Sheets(unaudited)(in thousands) September 30,2023 December 31,2022Assets Current assets: Cash and cash equivalents$99,986 $149,772 Prepaid expenses and other current assets 2,865 2,329 Short-term investments — 2,107 Total current assets 102,851 154,208 Property and equipment, net 27,851 30,039 Finance lease right-of-use assets, net 17,828 19,373 Other long-term assets 855 682 Total assets $149,385 $204,302 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable$3,018 $1,595 Accrued expenses 9,586 7,108 Other current liabilities 2,533 2,306 SVB loan payable, current portion — 8,571 Total current liabilities 15,137 19,580 Contingent earnout liability 39,601 27,893 Revenue interest liability 37,286 — Finance lease obligation, net of current portion 16,960 18,853 Other long-term liabilities 3,408 712 SVB loan payable, net of current portion — 20,336 Total liabilities 112,392 87,374 Stockholders’ equity Common stock and additional paid-in capital 549,201 543,466 Accumulated deficit (512,208) (426,538)Total stockholders’ equity 36,993 116,928 Total liabilities and stockholders’ equity$149,385 $204,302

GE HealthCare announced it signed a $44 million contract with the Biomedical Advanced Research and Development Authority ( BARDA ) to develop AI-enabled point-of-care ultrasound technology to help clinicians diagnose and treat lung pathologies and traumatic injuries to the head, chest and abdomen. The medtech company will build off its existing ultrasound technology to develop an AI-powered advanced probe and ultrasound system aimed at helping clinicians quickly triage and diagnose head trauma, blunt and penetrating trauma, multiple lung pathologies and lung injuries, including blast lung. BARDA is part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services ( HHS ), and the collaboration aims to improve routine delivery of care and enhance national preparedness for mass casualty incidents. "Working with BARDA is another step toward realizing the enormous potential of ultrasound technology to help hospitals increase preparedness for mass casualty events, including a range of traumatic injuries and lung pathologies, as well as help improve treatment decision-making and enhance patient care," Dietmar Seifriedsberger, global general manager of point of care and handheld ultrasound at GE HealthCare said in a statement. THE LARGER TREND GE completed the spin-off of its healthcare unit in January, and GE HealthCare has since made numerous announcements pertaining to acquisitions, partnerships and FDA clearance. The spin-off entered into an agreement to acquire French company IMACTIS , developer of computed tomography (CT) interventional guidance technology, the same month it became an independent company. A month later, it announced it acquired Caption Health , maker of AI-enabled ultrasound guidance software. Since its launch, GE HealthCare has received FDA 510(k) clearance for its Precision DL deep learning image-processing software and smartphone-sized Portrait Mobile wireless monitoring solution. Last month, the company secured a $44 million grant from the Bill and Melinda Gates Foundation to develop AI applications and tools to help healthcare providers in low- and middle-income countries perform ultrasound scans for fetal and maternal health and respiratory diseases. It also announced it had codeveloped an AI algorithm with Mass General Brigham to help with scheduling predictions and formed a strategic partnership with Mayo Clinic to collaborate on research and product development focusing on AI, precision care and theranostics.