Benign Paroxysmal Positional Vertigo

Hamilton, Bermuda, Sept. 24, 2024 (GLOBE NEWSWIRE) -- Company to host conference call today at 8.30 a.m. ETContinued progress within core activities in RNA delivery, supported by move into new R&D facilities Publications by independent research groups provide fresh evidence of effective mRNA delivery to extrahepatic targets Major territory expansion with two distribution partners for Bentrio® Financial results presented for first time in US dollars rather than Swiss francs Altamira Therapeutics Ltd. (“Altamira” or the “Company”) (Nasdaq:CYTO), a company dedicated to developing and commercializing RNA delivery technology for targets beyond the liver, today provided a business update and reported its first half 2024 financial results. "We are excited to continue to gain momentum with our new core activities in RNA delivery," commented Thomas Meyer, Altamira Therapeutics' founder, Chairman, and CEO. "Fresh in vivo data, recently published in a top-ranking scientific journal, show dramatic reductions in sarcoma and breast cancer growth following treatment with Zbtb46 mRNA delivered with our SemaPhore nanoparticle technology. The antitumor effect was further augmented when combined with anti-PD1 treatment. These impressive outcomes add to the growing body of evidence supporting the great potential of RNA therapeutics and the ability of our platform to deliver RNA molecules effectively and safely into target cells outside the liver, especially in cancer and inflammatory diseases.” Mr. Meyer added: “We are progressing with the development of both the OligoPhore and the SemaPhore platforms as well as with our AM-401 and AM-411 flagship programs in KRAS driven cancers and in rheumatoid arthritis, benefiting from our new access to laboratory space at the Switzerland Innovation Park in the Basel area. At the same time, we are evaluating our platforms for use in cardiac regeneration and for mRNA vaccines in joint projects with two partners and pursuing additional collaboration opportunities with other pharma and biotech companies. Further, we keep working towards completion of our strategic repositioning around RNA delivery through partnering of our legacy assets in inner ear therapeutics. Lastly, thanks to the recent public offering of shares, we have been able to strengthen our financial position for our transition to a much less capital-intensive business model based on contract development and licensing of our RNA delivery technology.” RNA Delivery Technology Research and development activities in Altamira’s core business of RNA delivery – built on its peptide based OligoPhore™ and SemaPhore™ nanoparticle platforms – continue to progress. The key focus is on nanoparticle formulation and process development around the platforms, the evaluation and development of nanoparticles for delivery of specific siRNA or mRNA payloads for collaboration partners, and the two flagship programs AM-401 or AM-411 for treatment of KRAS driven cancers and rheumatoid arthritis (RA), respectively. In August 2024, part of the Company’s expanding research and development team moved to the Switzerland Innovation Park in Allschwil near Basel. At the new location, the Company has access to modern and well-equipped lab facilities to support its growing activities. Evidence for the effectiveness and versatility of Altamira’s RNA delivery platforms keeps growing, as shown by two recent scientific publications: In a peer reviewed article in Nature Immunology, a research group from Washington University, St. Louis, MO, showed that systemic delivery of Zbtb46 mRNA with SemaPhore nanoparticles in mouse models of sarcoma and metastatic breast cancer resulted in sustained Zbtb46 expression, a restored immunostimulatory tumor microenvironment and a highly significant reduction in tumor growth (p<0.0001).1 When combined with an immune checkpoint inhibitor (anti-PD1) treatment, outcomes were even more pronounced. According to the authors, the “Zbtb46 nanoparticles induced dramatic anti-PD1 response in both anti-PD1-responsive [sarcoma] and anti-PD1-refractory [breast cancer] tumor models, generating long-term complete remission of tumor in many of the treated animals.” Extended monotherapy with Zbtb46 nanoparticles produced complete remission even in mice refractory to anti-PD1 treatment. Mice whose sarcoma was eliminated through treatment did not develop additional tumors following repeated challenge, indicating the development of a protective immunological memory. Another research group from Washington University presented in a preprint publication the results of a study showing that treatment with Sod2 mRNA delivered systemically with SemaPhore nanoparticles to mice with abdominal aortic aneurysm (AAA) resulted in a significant reduction in aorta dilation (p<0.05), delayed rupture and a significant improvement in survival rates (p<0.01).2 AAA is an inflammatory disease involving oxidative stress caused by excessive levels of reactive oxygen species, which results in an abnormal enlargement (bulge) of the abdominal aorta. AAA rupture may be life-threatening. Meanwhile, Altamira’s own development work has resulted in significant enhancement of nanoparticle stability, which has been one of the key challenges in the handling and transport of RNA formulations. Thanks to its new flow process production method, the Company obtained formulations of OligoPhore nanoparticles which are stable in liquid form when stored at 4°C for a period of at least one month. These formulations were, in addition, able to withstand shaking stress without significant physicochemical changes. The ability of nanoformulations to maintain their attributes during shaking stress is essential for transportation and one of the key limitations of lipid nanoparticles, the most common type of RNA delivery vehicles. For its proprietary development programs AM-401 and AM-411, Altamira filed in the first half of 2024 patent applications with the US Patent and Trademark Office. These aim to complement the existing intellectual property and extend the duration of protection. For AM-401, coverage of different KRAS mutations in cancer treatment with nanoparticles comprising the OligoPhore platform and a single siRNA sequence, polyKRASmut is sought. In vitro data confirmed the ability of polyKRASmut siRNA to knock down KRAS carrying the following mutations: G12C, G12V, G12D, G12R, G12A, and A146T, which account for the majority of KRAS mutations in pancreatic, colorectal and non-small cell lung cancer. For AM-411, coverage of nanoparticles comprising siRNA sequences targeting the p65 protein, a component of the NF-κB transcription factor, and OligoPhore is sought. Activation of p65 has been observed in multiple types of cancer as well as in many inflammatory diseases. For instance, p65 is a well-known key checkpoint in RA inflammation, and thought to regulate cell proliferation, cell death, and stimulate metastasis in cancer. The Company aims to advance both AM-401 and AM-411 to an Investigational New Drug (IND) filing with the Food and Drug Administration (FDA) in 2026 and to out-license them either following the IND or after a Phase 1 clinical trial at the latest. Altamira is pursuing with the RNA delivery business a ‘picks and shovels’ strategy based on the licensing of its platform technology to partners in the biotech and pharma industry for use in their own RNA drug product development programs. The first such collaborations have been set up: With Heqet Therapeutics s.r.l., a spin-out from King’s College London, Altamira is working on nanoparticles based on the OligoPhore platform and comprising certain non-coding RNAs (ncRNAs) for the regeneration of damaged heart tissue following myocardial infarction in animal models. With Belgium-based Univercells Group Altamira is evaluating the use of the SemaPhore platform for the delivery of mRNA vaccines. Thanks to lower mRNA loss during cell entrance, the nanoparticles may allow for using lower doses and thus result in potentially more effective and efficient vaccines. Upon positive outcomes from these evaluations, Altamira and its partners intend to discuss and negotiate licensing agreements. Through its business development activities, the Company is pursuing additional collaboration opportunities with other pharma and biotech companies. Bentrio® Nasal Spray The Company’s associate Altamira Medica AG (“Medica”) made further progress on implementing its growth strategy with Bentrio®, a drug free, preservative free nasal spray for the treatment of allergic rhinitis. With two of its international distributors, it recently agreed on the expansion of their exclusive distribution territories: With Nuance Pharma (“Nuance”) to extend the territory across South East and East Asia. Under the amended agreement, Nuance’s territory will expand from China, Hong Kong, Macau and South Korea to also include Singapore, Malaysia, Thailand, the Philippines, Indonesia, Vietnam and Taiwan, with a combined population of greater than 630 million people. Nuance has been marketing Bentrio since late 2022 in Hong Kong and recently submitted the request for marketing approval for Mainland China.With Pharma Nordic to extend the territory from Norway to also include Sweden and Denmark, which together have a population of 16.5 million. Pharma Nordic launched Bentrio successfully in Norway in 2024 and intends to introduce the product to Sweden and Denmark in 2025. In addition, discussions and negotiations for distribution in the US, Europe and other key markets are ongoing. The efficacy and safety of Bentrio has been demonstrated in a total of four clinical trials. Results from the largest among them (the “NASAR” study), which enrolled 100 patients suffering from seasonal allergic rhinitis in Australia, were recently published in a peer reviewed article in one of the leading scientific journals in allergology.3 In NASAR, participants self-administered either Bentrio or saline nasal spray for two weeks 3 times per day. The study showed a statistically significant reduction in the mean daily reflective Total Nasal Symptom Score (rTNSS) for Bentrio compared to saline (p = 0.013), as well as a statistically highly significant improvement in health-related quality of life (Rhinoconjunctivitis Quality of Life Questionnaire, p < 0.001) and superior global ratings of efficacy by patients and investigators alike (p < 0.001). In addition, Bentrio showed good safety and tolerability, similar to saline controls, and fewer Bentrio treated patients used relief medication and more of them enjoyed symptom-free days compared to saline treatment. In the context of its strategic pivot towards RNA delivery, Altamira divested in November 2023 a 51% stake in Medica to a Swiss private equity investor for a cash consideration of approximately $2.3 million. Altamira will be entitled to receive 25% of the future licensing income of Medica and of Medica’s value appreciation in case of a sale, which captures an additional share of the business’ upside potential. Inner Ear Therapeutics Altamira continues to work towards the partnering of its inner ear therapeutics assets, in particular AM-125, a patented nasal spray for the treatment of acute vestibular syndrome (AVS), which may be developed also for various other disorders of the central nervous system. AM-125 is a reformulation of betahistine, a histamine analog, which – in the traditional oral formulation – is the standard of care treatment for vertigo in many countries around the world. A phase 2 clinical trial in Europe demonstrated that a four-week treatment course with AM-125 in AVS patients was well tolerated and helped to accelerate vestibular compensation, enabling patients to regain balance and recover faster. In the U.S., where oral betahistine exceptionally has not been marketed for decades, Altamira received in summer 2023 IND clearance from the FDA for a phase 2 clinical trial in benign paroxysmal positional vertigo (BPPV), the most frequent type of AVS. BPPV accounts for 17 to 42% of all diagnosed cases; U.S. healthcare costs associated with the diagnosis of BPPV alone approach $2 billion per year.4 Continued simplification of group structure Following the partial divestiture of the Bentrio activities in late 2023, Altamira has continued its efforts to simplify its corporate structure and align it with the strategic repositioning around its RNA delivery platform. The Company transferred its Irish subsidiary Auris Medical Ltd. to Altamira Medica AG and merged two of its subsidiaries in Basel (Switzerland), Auris Medical AG and Altamira Therapeutics AG. The merged entity is called Altamira Therapeutics AG and continues to serve as the core operating subsidiary of the Company. Following this restructuring, the Altamira Group comprises the parent company Altamira Therapeutics Ltd. (Hamilton, Bermuda), and its subsidiaries Altamira Therapeutics AG (Basel, Switzerland), Altamira Therapeutics Inc. (Newark DE, USA), Otolanum AG (Basel, Switzerland) as well as the associated company Altamira Medica AG (Basel, Switzerland). First Half 2024 Financial Results and Outlook Following the partial divestiture of the Bentrio business, related activities have been reclassified and are reported as discontinued operations. Continuing operations thus comprise the RNA delivery development programs as well as those related to AM-125. The financial results are reported for the first time in US dollars, which the Company adopted as its new presentation currency, replacing the Swiss franc. Total operating loss from continuing operations was $3.9 million in the first half of 2024, compared against $3.6 million in the first half of 2023. The increase was primarily related to higher expenditures on research and development (+32.6% to $2.0 million), which was partially compensated by lower general and administrative expenses (-11.7% to $2.0 million). Net loss from continuing operations reached $4.3 million in the first half of 2024, which was 4.0% lower than in the corresponding reporting period in 2023. Finance expense decreased markedly ($0.2 million vs. $0.9 million); on the other hand, the Company recorded a pro rata loss of its associate company Altamira Medica of $0.2 million (first half of 2023: none)5. The Company’s net loss for the first half of 2024 amounted to $4.3 million, which was 27.0% lower than in the first half of 2023 ($5.9 million). During the first six months of 2023 the Company had recorded an after-tax loss of $1.4 million from discontinued operations (first half of 2024: none)5. Cash used in operations decreased from $8.4 million in the first half of 2023 to $3.2 million in the first half of 2024. Financing activities provided $8.4 million in the first six months of 2023 vs. $2.5 million in the first six months of 2024. Cash and cash equivalents on June 30, 2024 totaled $65 thousand compared with $55 thousand at June 30, 2023.Shareholders’ equity amounted to $6.3 million as of June 30, 2024 compared with $7.7 million at year-end 2023. There was no financial debt outstanding at either timepoint. Altamira expects total cash needs in 2024 to be in the range of $5.8 million to $7.0 million. During the third quarter of 2024, the Company raised $0.7 million from share issuances under the 2022 Commitment Purchase Agreement with Lincoln Park Capital Fund and gross proceeds of $4.0 million upfront from a public offering of common shares with milestone-linked warrants. First Half 2024 and Business Update Conference Call & Webcast Details Altamira’s Senior Management will hold an investor call today, Tuesday, September 24, 2024, at 8:30 a.m. EDT its business update and first half 2024 results. Founder, Chairman, and CEO Thomas Meyer and COO Covadonga Pañeda will deliver prepared remarks followed by a Q&A session where they will address questions from investors and analysts. Event: Altamira Therapeutics First Half 2024 Financial Results and Business Update CallDate: Tuesday, September 24, 2024Time: 8:30 am EDT Webcast URL: https://edge.media-server.com/mmc/p/4wp8659n Registration for Call https://register.vevent.com/register/BI039aac00f0eb4f228e9662f9b90a1ea4Click on the call link and complete the online registration form.Upon registering you will receive the dial-in info and a unique PIN to join the call as well as an email confirmation with the details.Select a method for joining the call: Dial-In: A dial in number and unique PIN are displayed to connect directly from your phone.Call Me: Enter your phone number and click “Call Me” for an immediate callback from the system. The call will come from a US number. Conference Call Replay A replay of the call will be available after the live event and accessible through the webcast link: https://edge.media-server.com/mmc/p/4wp8659n Consolidated Statement of Profit or Loss and Other Comprehensive Income/(Loss) For the six months ended June 30, 2024 and 2023 (in US$) Six months ended June 30 2024 20231) 2) Other operating income 34,298 77,474 Research and development (1,963,664) (1,480,708) General and administrative (1,987,972) (2,252,587) Operating loss (3,917,338) (3,655,821) Finance expense (186,000) (937,585) Finance income 513 69,540 Share of loss of an associate (237,007) - Net loss from continuing operations (4,339,832) (4,523,866) Discontinued operations: Loss after tax from discontinued operations - (1,420,862) Net loss attributable to owners of the Company (4,339,832) (5,944,728) Other comprehensive income/(loss): Items that will never be reclassified to profit or loss Remeasurements of defined benefit liability, net of taxes of $0 198,277 (31,634) Items that are or may be reclassified to profit or loss Foreign currency translation differences, net of taxes of $0 14,662 (80,121) Share of other comprehensive income of an associate (43,712) - Other comprehensive income/(loss), net of taxes of $0 169,227 (111,755) Total comprehensive loss attributable to owners of the Company (4,170,605) (6,056,483) Basic and diluted loss per share3) (2.11) (28.31) Basic and diluted loss per share from continuing operations3) (2.11) (21.55) 1) Amounts have been re-presented from those previously published to reflect the change in the Company’s presentation currency from Swiss francs to US dollars 2) Revised for the reclassification of certain activities as discontinued operations. 3) Weighted average number of shares outstanding: first half 2024: 2,060,714; first half 2023: 209,955. Consolidated Statement of Financial Position As of June 30, 2024 and December 31, 2023 (in US$) June 30, June 30, 2024 2023 1) ASSETS Non-current assets Property and equipment 1 1 Right-of-use assets 417,619 95,198 Intangible assets 4,627,072 4,627,072 Other non-current financial assets 88,999 95,070 Investment in an associate 2,411,469 2,872,623 Total non-current assets 7,545,160 7,689,964 Current assets Other receivables 121,310 88,916 Prepayments 75,213 337,293 Derivative financial instruments 262,035 293,630 Cash and cash equivalents 65,455 733,701 Total current assets 524,013 1,453,540 Total assets 8,069,173 9,143,504 EQUITY AND LIABILITIES Equity Share capital 5,341 2,956 Share premium - 23,889,332 Other reserves 5,054,761 5,129,585 Retained earnings/(Accumulated deficit) 1,258,213 (21,346,630) Total shareholders’ equity/(deficit) attributable to owners of the Company 6,318,315 7,675,243 Non-current liabilities Non-current lease liabilities 304,053 - Employee benefit liability 218,940 411,917 Total non-current liabilities 522,993 411,917 Current liabilities Current lease liabilities 123,384 118,430 Trade and other payables 526,571 523,367 Accrued expenses 577,910 414,547 Total current liabilities 1,227,865 1,056,344 Total liabilities 1,750,858 1,468,261 Total equity and liabilities 8,069,173 9,143,504 1) Amounts have been re-presented from those previously published to reflect the change in the Company’s presentation currency from Swiss francs to US dollars About Altamira Therapeutics Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a 49% stake (with additional economic rights) in Altamira Medica AG, which holds its commercial-stage legacy asset Bentrio®, an OTC nasal spray for allergic rhinitis. Further, the Company is in the process of partnering / divesting its inner ear legacy assets. Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/ Forward-Looking Statements This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Altamira’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to the clinical utility of Altamira’s product candidates, the timing or likelihood of regulatory filings and approvals, Altamira’s intellectual property position and Altamira’s financial position. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Altamira’s Annual Report on Form 20-F for the year ended December 31, 2023, and in Altamira’s other filings with the Securities Exchange Commission (“SEC”), which are available free of charge on the SEC’s website at: www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Altamira or to persons acting on behalf of Altamira are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Altamira does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. Investor Contact: Hear@altamiratherapeutics.com 1 Kabir AU et al. (2024), ZBTB46 coordinates angiogenesis and immunity to control tumor outcome, Nat Immunol https://www.nature.com/articles/s41590-024-01936-4. 2 Yan et al. (2024), Systemic delivery of murine SOD2 mRNA to experimental abdominal aortic aneurysm mitigates expansion and rupture, bioRxiv: 2024.06.17.599454. https://www.biorxiv.org/content/10.1101/2024.06.17.599454v1. 3 Becker S et al. (2024), AM-301, a barrier-forming nasal spray, versus saline spray in seasonal allergic rhinitis: A randomized clinical trial, Allergy 79(7):1858-67. https://onlinelibrary.wiley.com/doi/10.1111/all.16116 4 Özgirgin et al. (2024), Residual dizziness after BPPV management: exploring pathophysiology and treatment beyond canalith repositioning maneuvers, Front Neurol 15:1382196. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1382196/full 5 Altamira Medica was deconsolidated and classified as associate upon its partial divestiture in November 2023.

Hamilton, Bermuda, June 20, 2024 (GLOBE NEWSWIRE) -- Independent review discusses evidence supporting the use of betahistine to alleviate residual dizziness following physical repositioning procedures in benign paroxysmal positional vertigo (BPPV) patients Betahistine is marketed world-wide, except in the US, and considered standard of care treatment for dizziness / vertigo AM-125 is a nasal spray formulation of betahistine currently being developed by Altamira to overcome low bioavailability of oral formulation and make treatment option also available to US patients Altamira intends to partner or divest AM-125 as part of legacy assets in strategic pivot to RNA delivery technology Altamira Therapeutics Ltd. (“Altamira” or the “Company”) (Nasdaq:CYTO), a company dedicated to developing and commercializing RNA delivery technology for targets beyond the liver, today highlighted the publication of an article describing the rationale for and use of betahistine in the treatment of residual dizziness following standard of care physical repositioning procedures for benign paroxysmal positional vertigo (BPPV). The peer reviewed article was published by an international group of medical and scientific experts in vestibular disorders in the journal Frontiers in Neurology1 and reviews the potential causes of residual dizziness, which has been reported to occur in 31-61% of patients, and available treatment options. BPPV is characterized by repeated episodes of vertigo produced by changes in the head position relative to gravity, e.g. when tipping the head backward. It is typically caused by dislodged inner ear particles (otoconia) in one of the semicircular canals, most often the posterior canal. The debris elicits unwanted vestibular stimulation and is often cleared through physical repositioning procedures such as the Epley maneuver, which is strongly recommended by the Clinical Practice Guideline of the American Academy of Otolaryngology–Head and Neck Surgery. BPPV is the most common type of vertigo and accounts for 17 to 42% of all diagnosed cases; in the United States, healthcare costs associated with the diagnosis of BPPV alone approach $2 billion per year. Patients suffering from BPPV experience significant inconveniences and disabilities during symptomatic episodes, as they interfere with day-to-day activities such as driving a car or climbing stairs. Almost 86% of BPPV patients suffer some interruption to their daily activities and lost days at work due to BPPV. The dysfunction generally emerges in the elderly with a peak onset in the 5th and 6th decade. Even in case of a successful physical repositioning procedure, patients may experience residual dizziness. This may last for a few days up to several weeks and may affect quality of life and be of incapacitating nature. Residual dizziness may be due to, among others, remaining otoconia, incomplete vestibular compensation or microcirculation dysfunction. Based on their review of available treatment options, the authors of the publication suggest the use of vestibular habituation therapies and vestibular rehabilitation programs to facilitate vestibular compensation and treatment with betahistine for improvement of inner ear blood supply and promotion of vestibular compensation. An earlier publication by another research group had already shown in a meta-analysis that the combination of a common physical repositioning procedure with betahistine treatment resulted in a significantly greater reduction in dizziness handicap compared to the procedure alone (p = 0.001).2 “We welcome the additional research into residual dizziness after physical repositioning procedures in BPPV since this is a very common and oftentimes serious problem for patients”, commented Thomas Meyer, PhD, Altamira’s founder, chairman and CEO. “Treatment of BPPV is the single most important vestibular indication for betahistine, and we look forward to testing our AM-125, an intranasal formulation of the drug, specifically in this condition. AM-125 has a significantly higher bioavailability than the oral form of betahistine, which is currently marketed around the world, except for the US. As we are repositioning the Company around our RNA delivery technology, we are working towards the partnering of the program with one or several partners to take it forward and making betahistine ultimately also available to dizziness patients in the US.” About Betahistine Betahistine, a small molecule structural analog of histamine, acts as an agonist at the H1 histamine receptor and as an antagonist at the H3 histamine receptor. Unlike histamine, it crosses the blood-brain-barrier. Betahistine is known to increase the release of histamine, acetylcholine, dopamine and norepinephrine in the brain. It increases cochlear, vestibular and cerebral blood flow and facilitates vestibular compensation and inhibits neuronal firing in the vestibular nuclei. Betahistine for oral administration is approved in about 115 countries (with the U.S. being a notable exception) for the treatment of vertigo and Meniere’s disease. Despite its good safety profile, the clinical utility of orally administered Betahistine is limited due to poor bioavailability. About AM-125 AM-125 is an intranasal formulation of betahistine. Because of its ability to circumvent first-pass-metabolism, AM-125 has been shown to have 5-to-29 times higher bioavailability than orally administered betahistine. Altamira Therapeutics is developing AM-125 for the treatment of acute vestibular syndrome (AVS). The investigational drug has been tested successfully in a Phase 2 clinical trial (“TRAVERS”) with patients suffering from AVS following vestibular surgery: compared to placebo, AM-125 treatment helped accelerate vestibular compensation and alleviate signs and symptoms of vestibular dysfunction.3 About Altamira Therapeutics Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a 49% stake (with additional economic rights) in Altamira Medica AG, its commercial-stage legacy asset Bentrio®, an OTC nasal spray for allergic rhinitis. Further, the Company is in the process of partnering / divesting its inner ear legacy assets. Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: Forward-Looking Statements This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Altamira’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the success of strategic transactions, including licensing or partnering, with respect to Altamira’s legacy assets, Altamira’s need for and ability to raise substantial additional funding to continue the development of its product candidates, the clinical utility of Altamira’s product candidates, the timing or likelihood of regulatory filings and approvals, Altamira’s intellectual property position and Altamira’s financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Altamira’s capital structure, including future securities offerings. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Altamira’s Annual Report on Form 20-F for the year ended December 31, 2023, and in Altamira’s other filings with the Securities Exchange Commission (“SEC”), which are available free of charge on the SEC’s website at: Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Altamira or to persons acting on behalf of Altamira are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Altamira does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. Investor Contact: Hear@altamiratherapeutics.com 1 Özgirgin et al. (2024), Residual dizziness after BPPV management: exploring pathophysiology and treatment beyond canalith repositioning maneuvers, Front Neurol 15:1382196. 2 Li et al. (2023), Efficacy of Epley’s maneuver plus betahistine in the management of PC-BPPV - A systematic review and meta-analysis, Medicine (Baltimore) 102(13):e33421. 3 Van de Heyning et al. (2023), Efficacy and safety of intranasal betahistine in the treatment of surgery-induced acute vestibular syndrome: a double-blind, randomized, placebo-controlled phase 2 study, Otol Neurotol 44(5):493-501.

HAMILTON, BERMUDA, Sept. 12, 2023 (GLOBE NEWSWIRE) -- Company hosts 1H 2023 Financial Results and Business Update call today at 8 a.m. ET First research collaboration with biopharmaceutical company initiated for OligoPhore™ platform Partnering discussions for legacy assets progressing with conclusion of clinical development program and opening of IND as key milestones for Bentrio® and AM-125 Significant strengthening of shareholders’ equity and balance sheet Altamira Therapeutics Ltd. (NASDAQ:CYTO) ("Altamira" or the "Company"), a company dedicated to addressing unmet medical needs, today provided a business update and reported its first half 2023 financial results. "We continue progressing with the strategic repositioning toward becoming a leading provider of innovative RNA delivery technology," commented Thomas Meyer, Altamira Therapeutics' founder, Chairman, and CEO. "We have achieved great strides in enhancing awareness and visibility of our OligoPhore™ / SemaPhore™ platforms for extrahepatic RNA delivery and efficient endosomal release; as a result, we recently entered into our first collaboration with a biopharmaceutical company. We look forward to working with Heqet Therapeutics, in the framework of this first collaboration, on their mission to develop treatments for cardiac regeneration, applying RNA with our OligoPhore™ platform. We are excited to see interest in our technology growing steadily and remain confident about the potential to develop further partnerships with biopharmaceutical companies. "Meanwhile, we have reached important clinical and regulatory milestones in our legacy programs in OTC consumer health and inner ear therapeutics," Mr. Meyer added. "Our clinical trial with Bentrio in seasonal allergic rhinitis met the primary endpoint, adding further to our set of compelling efficacy data. In addition, the FDA cleared an IND for our AM-125 investigational drug in acute vestibular syndrome. These milestones are important elements in our ongoing partnering discussions.” “As part of our strategic pivot, we have adapted our organization, downsized activities especially in clinical development, and reallocated resources from our legacy programs towards our RNA delivery projects. This has allowed for a significant reduction in expense levels. At the same time, we have managed to significantly improve our shareholders’ equity position while reducing financial liabilities.” RNA Delivery Technology Altamira has continued to make progress with the further development of the RNA delivery technology around its OligoPhore™ / SemaPhore™ platforms, which are based on a patented peptide for delivery of RNA in nanoparticles to extrahepatic tissues and efficient endosomal release inside target cells. Two in vivo studies performed by independent research groups at Washington University School of Medicine (St. Louis, MO) using our SemaPhore™ platform provided further external validation of the technology. In a preprint, one research group presented animal data showing restriction of tumor growth with nanoparticles based on SemaPhore™ and ZBTB46 mRNA. Enforced ZBTB46 expression following treatment with the nanoparticles resulted in an immunostimulatory tumor microenvironment and restricted tumor growth. The effect was significantly potentiated when the treatment was combined with anti-PD1 immune checkpoint inhibition, suggesting that ZBTB46 mRNA delivered by SemaPhore™ nanoparticles could be an effective adjuvant therapy with immunotherapy in cancer management. Meanwhile, the other research group presented results from an animal study with DNMT3B mRNA nanoparticles based on Altamira's SemaPhore™ delivery technology at the Osteoarthritis Research Society International World Congress in Denver (CO). Local (intra-articular) administration of the nanoparticles to mice with meniscal injury resulted in strong induction of DNMT3B protein as well as significantly reduced bone sclerosis, cartilage degeneration, and synovitis (inflammation of the connective tissue lining the inside of a joint capsule). Functional studies showed significantly decreased pain sensitivity and improved weight bearing in active treated mice compared to controls. At the same time, the Company advanced work on its two flagship development programs AM-401, for the treatment of KRAS-driven tumors, and AM-411, for the treatment of rheumatoid arthritis; targeting NF-kB, aiming for an IND submission in 2024. Altamira plans to out-license the two programs either following the IND or after a Phase 1 clinical trial at the latest. Importantly, the Company filed a provisional patent application relating to single polyvalent siRNA sequences which as part of AM-401 can target different KRAS mutations (polyKRASmut). If granted, the patent would extend IP coverage for the program to 2043. In line with the Company’s strategy of leveraging the OligoPhore™/SemaPhore™ through out-licensing and partnering rather than commercializing its own drug products, Altamira has significantly expanded its business development activities. This includes the engagement of Maria Grunwald, PhD, MBA, a highly experienced business developer based in Boston, as Senior Business Advisor. On July 5, 2023 the Company announced that it entered into a collaboration and option agreement with Heqet Therapeutics s.r.l. (“Heqet”), a biotech spin-out from King’s College London. Under the terms of the agreement, Heqet will test nanoparticles based on Altamira’s OligoPhore™ delivery platform and comprising certain non-coding RNAs (ncRNAs) in the regeneration of damaged heart tissue following myocardial infarction in animal models. Upon successful conclusion of the experiments, Heqet will, under certain conditions, have the option to negotiate with Altamira for a license to use the Company’s technology and intellectual property to translate its findings into the development of therapeutics for cardiac regeneration. Bentrio® Nasal Spray On May 24, 2023, Altamira announced positive results from the randomized controlled NASAR clinical trial evaluating Bentrio® nasal spray in patients with seasonal allergic rhinitis (SAR). The NASAR trial enrolled 100 SAR patients in Australia who were randomized at a 1:1 ratio to receive either Bentrio® or saline nasal spray for two weeks via self-administration three times per day, or as needed. For eligibility, patients had to have a baseline reflective Total Nasal Symptom Score (rTNSS) of at least 5 points out of 12, referring to the worst level of nasal congestion, sneezing, nasal itching, and rhinorrhea (runny nose) within the past 24 hours averaged over a one-week treatment-free run-in period. The primary efficacy endpoint was defined as the difference in the average rTNSS over the subsequent 2-week treatment period between Bentrio® and saline nasal spray, the current standard of care in drug-free SAR management. The rTNSS decreased in the Bentrio® group from 6.9 points in the pre-treatment period to an average of 5.0 points over the 14-day treatment period (i.e. -1.9 points), while the saline spray group showed a decrease from 6.9 to 6.2 points (i.e. -0.8 points). The reduction in nasal symptoms conferred by Bentrio® was thus 2.4 times larger than with saline nasal spray. The difference in rTNSS reduction of 1.1 points in favor of Bentrio® was statistically significant in the ANCOVA model (LSmeans; p = 0.012; 95% confidence interval -2.0 to -0.3), and the study thus met the primary efficacy endpoint. 63.3% of Bentrio®-treated study participants rated treatment efficacy as either good or very good vs. 29.2% of saline-treated participants. 73.5% of Bentrio®-treated study participants rated tolerability of the treatment as either good or very good vs. 85.5% of saline-treated participants. The Company expects to release further results from the NASAR trial shortly and to submit an article for publication in a peer-reviewed medical journal. The data read-out from the NASAR trial completes the Bentrio® development program in allergic rhinitis. Previous clinical trials demonstrated the safety, tolerability and efficacy of Bentrio in patients exposed to grass pollen or house dust mites under controlled conditions and the extended nasal residence time of more than three hours in human volunteers. The accumulated data suggest that Bentrio®, based on a drug-free and preservative-free formulation, can help to effectively reduce the most common symptoms of allergic rhinitis similar to the reduction observed in response to medicated nasal sprays, but without the tolerability issues frequently experienced with the use of such sprays. On July 20, 2023, Altamira announced that it entered into an exclusive agreement with Pharma Nordic AS for the marketing and distribution of Bentrio® in Norway and potentially further Scandinavian countries. The collaboration agreement will allow Pharma Nordic to market and commercialize Bentrio® in Norway beginning in the first quarter of 2024, and, subject to meeting certain milestones, also in Sweden, Finland, and Denmark later on. Discussions with potential marketing and distribution partners for the US and other key markets have continued to move forward and are still ongoing at this time. In the context of these partnering discussions, it has suspended preparations for launching the product in the US on its own and minimized marketing and sales activities in Europe. Inner Ear Therapeutics On June 29, 2023, the FDA completed its review of Altamira’s IND application for AM-125 (betahistine nasal spray) in acute vestibular syndrome (AVS) and concluded that the proposed Phase 2 clinical trial with AM-125 in the treatment of posterior canal benign paroxysmal positional vertigo (BPPV), the most common type of vertigo, may proceed. The regulatory clearance opened the way for the clinical evaluation of AM-125 also in the United States. An earlier Phase 2 clinical trial conducted in Europe (the TRAVERS trial) demonstrated that a four-week treatment course with AM-125 in AVS patients, following surgical removal of a tumor behind the inner ear, was well tolerated and helped to accelerate vestibular compensation enabling patients to regain balance and recover faster. The new Phase 2 trial is designed to demonstrate AM-125’s tolerability and clinical utility also in BPPV. As previously announced, Altamira intends to divest or partner the AM-125 program for further development and commercialization in the context of its strategic pivot to RNA delivery technology. To this end, the Company has initiated discussions with a number of potential partners based on a structured approach. First Half 2023 Financial Results and Financial Guidance Revenues for the first half of 2023 were CHF 0.1 million compared to CHF 0.3 million for the first half of 2022, reflecting the waning of SARS-CoV-2 infections and, more importantly, the aforementioned strategic decision to temporarily reduce commercial activities around Bentrio® in anticipation of partnering transactions for key markets. Total operating loss for the first six months of 2023 was CHF 4.6 million compared with CHF 8.4 million for the first six months of 2022, a reduction of 45.5%. The improvement was primarily driven by lower expenditures for research and development (CHF 2.3 million vs. CHF 3.6 million) as clinical trials wound down, and for marketing and sales (CHF 0.2 million vs. CHF 2.1 million) as commercial activities were reduced. General and administrative expenses slightly increased in the first half of 2023 to CHF 2.2 million from CHF 2.1 million in the first half of 2022 as higher costs related to capital market projects outweighed reductions in administrative expenditures. Net loss for the first half of 2023 was CHF 5.4 million compared with CHF 8.2 million for the first half of 2022. Financial liabilities decreased from CHF 5.9 million at the end of 2022 to CHF 3.1 million at June 30, 2023. Shareholders’ equity improved at the same time from CHF -8.3 million to CHF -1.8 million. Cash and cash equivalents on June 30, 2023 totaled CHF 50 thousand compared with CHF 15 thousand at December 31, 2022. In early July 2023 Altamira raised $5.0 million in equity through the public offering of 11,111,112 common shares (or pre-funded warrants) at $0.45 each and 11,111,112 warrants with an exercise price of CHF 0.40 and a 5-year duration. The transaction yielded net proceeds of CHF 3.7 million. The Company expects its total cash need in 2023 to be in the range of CHF 12 to 14 million and in the 12 months from the issuance date of these financial statements to be in the range of CHF 12 to 14 million. First Half 2023 Investor Conference Call & Webcast Details Altamira management will hold an investor teleconference today, Tuesday, September 12, 2023, at 8:00 a.m. ET to discuss its business update and first half 2023 results. Founder, Chairman, and CEO Thomas Meyer and COO Covadonga Pañeda will deliver prepared remarks followed by a Q&A session where they will address questions from investors and analysts. Event: Altamira Therapeutics First Half 2023 Financial Results and Business Update CallDate: Tuesday, September 12thTime: 8am ET (5am PT) Access: Toll Free: 888-506-0062International: 973-528-0011Participant Access Code: 500382Webcast URL: https://www.webcaster4.com/Webcast/Page/2797/48993 Investors can begin accessing the webcast 15 minutes before the call, where an operator will register your name and organization. The call will be in listen-only mode. A replay of the call will be available 30 minutes after the live call via the Investors section of the Altamira website at https://ir.altamiratherapeutics.com/. Replay Access:Toll Free replay number: 877-481-4010International: 919-882-2331Replay Passcode: 48993Expiration: September 26, 2023, 11:59 PM ET Condensed Consolidated Interim Statement of Profit or Loss and Other Comprehensive Income or Loss (unaudited) For the Six Months Ended June 30, 2023 and 2022 (in CHF) SIX MONTHS ENDED JUNE 30 2023 2022 Revenue 105,469 290,798 Cost of Sales (212,181) (1,192,232)Gross profit (106,712) (901,434)Other operating income 111,405 255,820 Research and development (2,261,154) (3,563,883)Sales and marketing (160,936) (2,129,881)General and administrative (2,168,953) (2,076,383)Operating loss (4,586,350) (8,415,761)Finance expense (861,118) (377,985)Finance income 37,018 509,143 Loss before tax (5,410,450) (8,284,603)Income tax gain/(loss) (10,596) 46,085 Net loss attributable to owners of the Company (5,421,046) (8,238,518)Other comprehensive income: Items that will never be reclassified to profit or loss Remeasurement of defined benefit liability, net of taxes of CHF 0 (28,847) 209,526 Items that are or may be reclassified to profit or loss Foreign currency translation differences, net of taxes of CHF 0 137,747 (63,477)Other comprehensive income, net of taxes of CHF 0 108,900 146,049 Total comprehensive loss attributable to owners of the Company (5,312,146) (8,092,469) Condensed Consolidated Interim Statement of Financial Position (unaudited) As of June 30, 2023 and December 31, 2022 (in CHF) JUNE 30, DECEMBER 31, 2023 2022 ASSETS Non-current assets Property and equipment 1 1 Right-of-use assets 387,737 445,827 Intangible assets 3,893,681 3,893,681 Other non-current financial assets 192,958 194,263 Total non-current assets 4,474,377 4,533,772 Current assets Inventories 270,503 11,644 Trade receivables 31,813 6,525 Other receivables 756,234 755,987 Prepayments 374,376 709,266 Derivative financial instruments 247,090 270,176 Cash and cash equivalents 49,569 15,395 Total current assets 1,729,585 1,768,993 Total assets 6,203,962 6,302,765 EQUITY AND LIABILITIES Equity Share capital 1,590,801 236,011 Share premium 15,560,642 192,622,406 Other reserves 871,633 258,044 Accumulated deficit (19,847,641) (201,431,272)Total shareholders’ equity attributable to owners of the Company (1,824,565) (8,314,811) Non-current liabilities Loan 930,561 - Non-current lease liabilities 287,808 343,629 Employee benefits 381,362 336,206 Deferred income 932,200 932,200 Deferred tax liabilities 129,291 125,870 Total non-current liabilities 2,661,222 1,737,905 Current liabilities Loan 2,130,340 5,869,797 Current lease liabilities 118,229 117,856 Trade and other payables 1,964,139 4,914,404 Accrued expenses 1,154,598 1,977,614 Total current liabilities 5,367,305 12,879,671 Total liabilities 8,028,527 14,617,576 Total equity and liabilities 6,203,962 6,302,765 About Altamira TherapeuticsAltamira (Nasdaq: CYTO) is dedicated to developing RNA-based therapeutics for extrahepatic targets (OligoPhore™ / SemaPhore™ delivery platforms). The Company currently has two flagship siRNA programs in preclinical development beyond in vivo proof of concept: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis. The versatile delivery platform is also suited for mRNA and other types of RNA therapeutics and is planned to be leveraged via out-licensing to pharma or biotech companies. In addition, Altamira is in the process of divesting and/or out-licensing its legacy assets in allergology and viral infection (Bentrio® OTC nasal spray; commercial) and inner ear therapeutics (AM-125 nasal spray for vertigo; post Phase 2; Keyzilen® and Sonsuvi® for tinnitus and hearing loss; Phase 3). Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/ Forward-Looking StatementsThis press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Altamira’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the success of the continued commercialization of Bentrio and success of strategic transactions, including licensing or partnering, with respect to Bentrio or any other legacy assets, Altamira’s need for and ability to raise substantial additional funding to continue the development of its product candidates, the timing and conduct of clinical trials of Altamira’s product candidates, the clinical utility of Altamira’s product candidates, the timing or likelihood of regulatory filings and approvals, Altamira’s intellectual property position and Altamira’s financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Altamira’s capital structure, including future securities offerings. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Altamira’s Annual Report on Form 20-F for the year ended December 31, 2022, and in Altamira’s other filings with the Securities Exchange Commission (“SEC”), which are available free of charge on the SEC’s website at: www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Altamira or to persons acting on behalf of Altamira are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Altamira does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law.